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Abstract An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20–84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957–2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted.

The pathogenic role of p-ANCA in eosinophilic granulomatosis with polyangiitis (EGPA) is a long-standing matter of debate. In this work, we report our real-life experience with EGPA patients, treated with biologics targeting type 2 (T2)-eosinophilic inflammation (Mepolizumab, Benralizumab, Dupilumab). Interestingly, we observed EGPA extrarespiratory relapses only in p-ANCA-positive patients (2/5 cutaneous vasculitis, 3/5 constitutional symptoms), with new rise of p-ANCA and normal eosinophil blood count. Notably, revising our cohort with the new ACR 2022 criteria, these five patients were the only ones to satisfy the entry criterion of vasculitis' defined diagnosis at disease onset. These observations may suggest that biologics, selectively turning off T2 inflammation, may have unmasked p-ANCA exclusive role in the pathogenesis of vasculitis in EGPA. Therefore, we raise the question whether EGPA vasculitis exists only in p-ANCA-positive patients, and whether p-ANCA-negative disease is "only eosinophils without vasculitis"., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Piga, Fraticelli, Antonicelli, Garritani, Ghirelli, Martini, Di Vincenzo, Danieli, Moroncini and Bilò.)

Summary: Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM 10 , PM 2.5 ), nitrogen dioxide (NO 2 ), and summer ozone (O 3 ) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 μg/m 3 (PM 10 ), 20.1 ± 5.6 μg/m 3 (PM 2.5 ), 27.2 ± 9.7 μg/m 3 (NO 2 ), and 70.8 ± 4.2 μg/m 3 (summer O 3 ). The concentrations of PM 10 , PM 2.5 , and NO 2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM 10 : OR 1.62, 95%CI: 1.19-2.20 and PM 2.5 : OR 1.80, 95%CI: 1.16-2.81, per 10 μg/m 3 ) and between NO 2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 μg/m 3 ), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO 2 , a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD., Competing Interests: Declaration of competing interest Sara Maio reports financial support was provided by National Institute for Insurance against Accidents at Work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Approximately 3-10% of people with asthma have severe asthma (SA). Patients with SA have greater impairment in daily life and much higher costs. Even if asthma affects the entire bronchial tree, small airways have been recognized as the major site of airflow limitation. There are several tools for studying small airway dysfunction (SAD), but certainly the most interesting is oscillometry. Despite several studies, the clinical usefulness of oscillometry in asthma is still in question. This paper aims to provide evidence supporting the use of oscillometry to improve the management of SA in clinical practice., Areas Covered: In the ATLANTIS study, SAD was strongly evident across all severity. Various tools are available for evaluation of SAD, and certainly an integrated use of these can provide complete and detailed information. However, the most suitable method is oscillometry, implemented for clinical routine by using either small pressure impulses or small pressure sinusoidal waves., Expert Opinion: Oscillometry, despite its different technological implementations is the best tool for determining the impact of SAD on asthma and its control. Oscillometry will also be increasingly useful for choosing the appropriate drug, and there is ample room for a more widespread diffusion in clinical practice.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene-Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (<2500 g), and this proportion was greater in women than men (7.8% vs. 5.1%; p = 0.006). Both men and women with low BW were shorter than those with normal BW (mean ± SD: 160.2 ± 5.5 vs. 162.6 ± 6.5 cm in women, p = 0.009; 172.4 ± 6.1 vs. 174.8 ± 7.2 cm in men, p < 0.001). Although FEV1 and FVC were reduced in individuals with low BW, this was explained by associations with sex and height. In multivariable analysis, BW was not associated with respiratory diseases in adulthood. However, those with low BW had a higher risk of self-reported hospitalisation for lung disease before the age of two (10.3% vs. 4.1%; p < 0.001), severe respiratory infection before the age of five (16.9% vs. 8.8%; p = 0.001) and hypertension in adulthood (29.9% vs. 23.7%; p = 0.001); however, they had a lower risk of arrhythmia (2.7% vs. 5.8%; p = 0.027).

Severe asthma patients' life is heavily influenced by the disease, which has impact on personal and professional choices or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative "Patients insight meeting" was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient's experience of his/her disease that need to be included in severe asthmatics' management strategy., (©Copyright: the Author(s).)

Introduction: Dupilumab is a monoclonal antibody targeting IL-4Rα recently licensed for severe asthma (SA). A Named Patients Program (NPP) was created in Italy before its commercial availability for SA patients with no other available therapeutic options. We aimed to assess the real-world effectiveness of dupilumab in patients with SA and unmet needs., Methods: We performed a multicentre retrospective study, including SA patients admitted to the NPP treated with dupilumab for 12 months. Data on the number of exacerbations, Asthma Control Test (ACT), pre-bronchodilator FEV 1 %, oral corticosteroids (OCSs) use, FeNO and eosinophils count in peripheral blood were recorded at baseline and after 3, 6, and 12 months., Results: We included 18 SA patients (mean age 53.3±12.4 years, 66.7% female). Eleven (61.1%) were OCSs dependent. Five patients (27.8%) received previous anti-IgE and/or anti-IL-5 agents. A significant improvement in ACT score (from 15.7±5.1 to 18.8±4.8, p=0.023), OCSs intake [10 (5-25) mg/day to 0 (0-5) mg/day, p=0.0333] and FeNO [from 25 (20-80) ppb to 21 (10.9-55.3) ppb, p=0.0190] was already detected after 3 months of treatment. After 12 months, a statistically significant decrease in the number of exacerbations from 2 (0-3) to 0 (0-1) (p<0.0068) and increase in FEV 1 % from 73.5±19.5% to 87.1±19.2% (p=0.0407) and ACT to a mean value of 22.4±1.7 (p<0.0001) and the interruption of OCSs in all the patients (p<0.0001) was observed. A transient increase in the eosinophil count was observed in five patients (above 1000 cells/μL in 2 cases) after 3 months, without any clinical effect., Conclusion: Dupilumab improved all the explored clinical outcomes after 12 months, and the transient hypereosinophilia did not modify treatment response. These real-world data confirm the results reported in randomized controlled trials and provide an important opportunity to characterize the clinical impact of the treatment in a non-trial setting. Further real-world studies with a larger cohort of patients are needed to confirm these findings., Competing Interests: Prof. Dr. Alberto Papi reports grants from CHIESI, ASTRAZENECA, GSK, BI, PFIZER, TEVA, and SANOFI; personal fees from CHIESI, ASTRAZENECA, GSK, BI, MENARINI, NOVARTIS, ZAMBON, MUNDIPHARMA, TEVA, SANOFI, EDMOND PHARMA, IQVIA, MSD, AVILLION, and ELPEN PHARMACEUTICALS, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 Campisi et al.)

Summary: Background. The Italian Registry on Severe Asthma (IRSA) is the most recent and largestregistry in Italy. Objective. To improve the knowledge on the clinical and biological features of severe asthma (SA), and to monitor its treatments. Methods. To analyze clinical,functional, inflammatory, and treatment characteristics of severe asthmatics from the IRSA registry. Results. 851 subjects were enrolled. 31.8% and 64.5% of patients were submitted to oral corticosteroids (OCS), and monoclonal antibodies (MABs), respectively. At least tw ocomorbidities affected 77.4% patients. Asthma was uncontrolled in 62.2% patients. Uncontrolled patients had a higher frequency of exacerbations, and hospitalization, showing a highere osinophilic phenotype, a greater use of OCS, and being treated with MAB less frequently. However, uncontrolled patients treated with MAB had a lower use of OCS and a lower rateof hospitalization. Comparing SA patients with atopy and without atopy, the latter showeda greater use of OCS, and more frequent nasal polyposis and osteoporosis. Among SA patients with atopy treated with MAB, 36% were on a treatment targeting the IL-5 pathway. Conclusions and clinical relevance. This study shows the features of the greatest Italian registryof SA patients, revealing at the time of enrollment a poor disease control, and the use of OCSand MABs in about one third and two thirds of patients, respectively. SA is a complex diseasethat requires a more precise phenotyping and a greater disease control.

Background: Gastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated., Aims: To evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis., Methods: We investigated 2887 subjects aged 20-84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed "gastritis or stomach ulcer (confirmed by gastroscopy)" or "gastroesophageal reflux disease, hiatal hernia or esophagitis". The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression., Results: The prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56-5.62) and sinusitis (RRR = 3.70, 2.62-5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37-2.35).., Conclusion: The study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR.

Background: According to expert consensus, the time interval between Hymenoptera venom immunotherapy (VIT) injections can be extended up to 12 weeks, without significant impact on efficacy and safety. However, the coronavirus disease 2019 pandemic caused longer delays, and no recommendations are available to manage this huge extension., Objectives: To provide advice on how to resume VIT safely after a long delay from the last injection considering the potential risk factors for side effects, without starting again with the induction phase., Methods: All the patients who delayed VIT because of the pandemic were consecutively enrolled in this single-center study. The time extension was decided according to their risk profile (eg, long prepandemic time interval, severe pre-VIT reaction, older age, multitreatments), and correlation analyses were performed to find potential risk factors of side effects., Results: The mean delay from the pre- (7 weeks) to the postpandemic VIT interval (15.5 weeks) was 8.5 weeks. The total amount of the prepandemic VIT maintenance dose was safely administered in 1 day in 78% of patients, whereas only 3, of 87, experienced side effects, and their potential risk factors were identified in bee venom allergy and recent VIT initiation., Conclusions: In a real-world setting, long VIT delays may be safe and well tolerated, but more caution should be paid in resuming VIT in patients with long prepandemic maintenance interval, severe pre-VIT reaction, recent VIT initiation, older age, multidrug treatments, and bee venom allergy. This is useful in any case of long, unplanned, and unavoidable VIT delay., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, and it can be life-threatening or even fatal. It involves the activation of multiple immune and non immune pathways beyond IgE, thus exhibiting different phenotypes. New symptoms of hypersensitivity caused by chemotherapy drugs, monoclonal antibodies, and biological agents have been suggested to be recognized as anaphylaxis phenotypes. No biomarker has been described that allows an unequivocal diagnosis of anaphylaxis. Moreover, more biomarkers for specific endotypes are needed to stratify severity, to predict risk, and to optimaze tretament choice in the individual patient. Food, drugs and stinging insects represent the most commly identified triggers. Idiopathic anaphylaxis is a diagnosis of exclusion and it can hide a clonal mast cell disorder. Individual risk factors and co-factors may influence the severity of anaphylaxis or its onset, and they should be identified to implement the appropriate measures to prevent recurrence. Prompt recognition and treatment are critical in anaphylaxis, adrenaline being the first-line saving therapy. Individualized anaphylaxis action plan should include avoidance measures, prescription of an adrenaline autoinjector, education, optimal management of relevant comorbidities, venom specific immunotherapy, food oral immunotherapy, and drug desensitization, when appropriate. However, the quality of acute and long-term anaphylaxis management is variable influencing the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes, but they often prove challenging to implement in routine clinical care.

Background and Objectives: Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population., Methods: We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21-86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models., Results: Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12-2.22]) and rhinitis (1.35[0.98-1.85]) and intermittent claudication was associated with CB (3.43[2.52-4.67]), asthma (1.51[1.04-2.21]) and rhinitis (2.03[1.34-3.07])., Conclusions: CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication., Competing Interests: The authors have declared that no competing interests exist.

Summary: Hymenoptera venom allergy (HVA) is the most frequent cause of anaphylaxis in Europe, accounting for most of the severe reactions occurring in adults, and being the second cause of anaphylaxis in children. Prevention of further episodes in patients who developed a systemic reaction (SR) is based on the correct management of the allergic emergency, the referral to an allergist for a correct diagnosis, prescription of adrenaline auto-injectors (AAI) and specific venom immunotherapy (VIT), if recommended. Diagnosis is based on the classification of the type of reaction, confirmation of an IgE-mediated pathogenesis and the identification of the offending insect. The use of component resolved diagnostics may be helpful in case of poly-sensitization or negative allergy tests with a proven history of previous SRs. When a severe SR occurs, baseline serum tryptase levels should always be assessed. The prescription of AAI is recommended or suggested for untreated patients, patients undergoing VIT and after discontinuation of treatment, according to multiple evidence. VIT is the most effective treatment available for HVA patients, as confirmed by recent European guidelines. VIT has an early, sustained and persistent protective effect and modifies the natural course of the disease. Moreover, VIT proved to be safe and well tolerated. According to a recent systematic review, no treatment-related fatalities were recorded to date. Compared to AAI, VIT significantly improves the quality of life of HVA patients by reducing the anxiety and limitations in daily activities caused by the fear of stinging insects. The memory of a life-threatening experience is the most likely reason why adherence to VIT is higher compared to immunotherapy with inhalant allergens. Several risk factors in HVA have been identified that can influence not only the severity of sting reactions in untreated patents, but also the occurrence of side effects, treatment effectiveness and the risk of relapse after discontinuation of VIT. Patient and treatment-related risk factors must be considered while selecting the best candidates for VIT, the type and duration of treatment. In this paper we address the most important issues related to HVA and VIT that may have an impact on daily clinical practice.

Background: Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population., Methods: The data were collected in GEIRD, an Italian multicenter, population-based, multicase-control study. 2227 participants (age 21-86 years, female 50%) underwent standardized interviews, skin prick and lung function tests, and were divided into cases of current asthma (n = 528), rhinitis without asthma (n = 972), and controls (n = 727). Two specific questions from the Patient Health Questionnaire (PHQ-2) were asked to identify symptoms of depressed mood and anhedonia, which were used as a proxy of major depression disorder., Results: The prevalence of depression was 16.7%, 11.9%, and 5.1% in subjects with asthma, rhinitis and controls, respectively. Both in asthma and rhinitis, subjects with depression had worse respiratory-health related quality of life and more frequent disease-related symptoms than their non-depressed counterparts. In asthma, depression was associated with poorer disease control. In rhinitis, depression was significantly associated with a disease-related limitations in daily activities and greater risk of symptom exacerbations and prescriptions of medicines for breathing. Cases of rhinitis with depression were less likely to be atopic., Conclusions: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Summary: The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.

Background: The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care., Methods: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed., Results: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV 1 % pred of 75.1%, median values of 300/mm 3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations., Conclusions: An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Osteoarthritis is a whole-joint disease and its pathogenesis remains poorly understood. Recent evidence proposed the importance of the innate immune system as trigger of synovium inflammation following the degeneration of cartilage. Moreover, synovial mast cells (MCs) might be correlated with pain and disability reported by patients. Anti IgE therapy represents a new class of MCs stabilizing agent, licensed for people with asthma and chronic urticaria. Therefore, we studied if the stabilizing effect of anti IgE would improve the pain and disability in patients affected by knee osteoarthritis and atopic disease. This pilot study provides the first evidence that anti IgE treatment induces a short-term clinical improvement supporting the role of MCs in osteoarthritis.

Background: Pollen exposure has acute adverse effects on sensitized individuals. Information on the prevalence of respiratory diseases in areas with different pollen concentrations is scanty., Aim: We performed an ecologic analysis to assess whether the prevalence of allergic rhinitis and asthma in young adults varied across areas with different pollen concentrations in Italy., Methods: A questionnaire on respiratory diseases was delivered to random samples of 20-44year-old subjects from six centers in 2005-2010. Data on the daily air concentrations of 7 major allergologic pollens (Poaceae, Urticaceae, Oleaceae, Cupressaceae, Coryloideae, Betula and Ambrosia) were collected for 2007-2008. Center-specific pollen exposure indicators were calculated, including the average number of days per year with pollens above the low or high concentration thresholds defined by the Italian Association of Aerobiology. Associations between pollen exposure and disease prevalence, adjusted for potential confounders, were estimated using logistic regression models with center as a random-intercept., Results: Overall, 8834 subjects (56.8%) filled in the questionnaire. Allergic rhinitis was significantly less frequent in the centers with longer periods with high concentrations of at least one (OR per 10days=0.989, 95%CI: 0.979-0.999) or at least two pollens (OR=0.974, 95%CI: 0.951-0.998); associations with the number of days with at least one (OR=0.988, 95%CI: 0.972-1.004) or at least two (OR=0.985, 95%CI: 0.970-1.001) pollens above the low thresholds were borderline significant. Asthma prevalence was not associated with pollen concentrations., Conclusions: Our study does not support that the prevalence of allergic rhinitis and asthma is greater in centers with higher pollen concentrations. It is not clear whether the observed ecologic associations hold at the individual level., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Summary: Background. Anisakis simplex hypersensitive subjects may be sensitized without clinical allergy, or experience acute symptoms or chronic urticaria induced by raw fish. We studied whether the 3 subgroups differ in IgE, IgG 1 or IgG 4 reactivity to specific Anisakis simplex allergens. Methods. 28 Anisakis simplex-hypersensitive adults, 11 with acute symptoms, 9 with chronic urticaria, and 8 sensitized were studied. IgE, IgG 1 and IgG 4 to rAni s 1, 5, 9 and 10 were sought by ELISA. IgE and IgG 4 to nAni s 4 were determined by WB. Results. IgE to Ani s 1, 4, 5, 9, and 10 were found in 8, 3, 2, 5, and 9 sera, respectively. Nine sera did not react to any allergen. IgG 1 to Ani s 1, 5, 9, and 10 were detected in 5, 16, 14, and 4 sera, respectively. Four sera did not react to any of the 4 allergens. IgG 4 to Ani s 1, 4, 5, 9, and 10 were detected in 10, 0, 2, 6 and 1 sera, respectively. Fifteen subjects did not react to any of the 5 allergens. On ELISA sensitized subjects showed lower IgE and IgG 1 levels than patients. IgG 4 levels were highest in the sensitized group. The prevalence of IgE, IgG 1 or IgG 4 reactivity to any of the studied allergens did not differ between the 3 subgroups. Conclusion. The clinical expression of Anisakis simplex sensitization does not seem to depend on IgE reactivity to a specific allergen of the parasite, nor on the presence of IgG antibodies possibly related with blocking activity.

The clinical role of Ara h 6 sensitization in peanut allergy is a current matter of debate. We investigated the role of Ara h 6 sensitization patterns in a sample of young adults from different Italian cities. Sera of 33 patients with specific IgE against Ara h 6 were selected. According to clinical symptoms upon peanut ingestion, patients were divided into severe reaction (SR) and mild-tolerant (MT) subgroups. While the SR group mainly showed sensitization patterns involving Ara h 2 and other major allergenic components, a previously undescribed association between Ara h 6 and Ara h 9 was found in the MT group. This pattern seems to be clustered in Mediterranean Italy and associated with Pru p 3 sensitization. This finding might shed a new light on the role of Ara h 6 sensitization in peanut allergy.

Despite major advances in the treatment of asthma and the development of several asthma guidelines, people still die of asthma currently. According to WHO estimates, approximately 250,000 people die prematurely each year from asthma. Trends of asthma mortality rates vary very widely across countries, age and ethnic groups. Several risk factors have been associated with asthma mortality, including a history of near-fatal asthma requiring intubation and mechanical ventilation, hospitalization or emergency care visit for asthma in the past year, currently using or having recently stopped using oral corticosteroids (a marker of event severity), not currently using inhaled corticosteroids, a history of psychiatric disease or psychosocial problems, poor adherence with asthma medications and/or poor adherence with (or lack of) a written asthma action plan, food allergy in a patient with asthma. Preventable factors have been identified in the majority of asthma deaths. Inadequate education of patients on recognising risk and the appropriate action needed when asthma control is poor, deficiencies in the accuracy and timing of asthma diagnosis, inadequate classification of severity and treatment, seem to play a part in the majority of asthma deaths. Improvements in management, epitomized by the use of guided self-management systems of care may be the key goals in reducing asthma mortality worldwide.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Background: Several studies highlighted a great variability, both between and within countries, in the prevalence of asthma and chronic airways diseases., Aim: To evaluate if geo-climatic variations can explain the heterogeneity in the prevalence of asthma and respiratory diseases in Italy., Methods: Between 2006 and 2010, a postal screening questionnaire on respiratory health was administered to 18,357 randomly selected subjects, aged 20-44, living in 7 centers in northern, central, and southern Italy. A random-effects meta-analysis was fitted to evaluate the between-centers heterogeneity in the prevalence of asthma, asthma-like symptoms, allergic rhinitis, and chronic bronchitis (CB). A principal component analysis (PCA) was performed to synthetize the geo-climatic information (annual mean temperature, range of temperature, annual rainfalls, global solar radiations, altitude, distance from the sea) of all the 110 Italian province capital towns. The associations between these geo-climatic components obtained with PCA and the prevalence of respiratory diseases were analyzed through meta-regression models., Results: 10,464 (57%) subjects responded to the questionnaire. There was a significant between-centers heterogeneity in the prevalence of asthma (I(2)=59.5%, p=0.022) and CB (I(2)=60.5%, p=0.019), but not in that of asthma-like symptoms or allergic rhinitis. Two independent geo-climatic components explaining together about 80% of the overall geo-climatic variability were identified: the first principally summarized the climatic variables; the second the topographic ones. Variations in the prevalence of asthma across centers were significantly associated with differences in the climatic component (p=0.017), but not with differences in the topographic one., Conclusions: Our findings suggest that climate play a role in determining the between-center heterogeneity in the prevalence of asthma in Italy, with higher prevalence in dry-hot Mediterranean climates, and lower in rainy-cold northern climates., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Few population-based studies have assessed the prevalence and the risk factors of non-allergic rhinitis (NAR) in comparison to allergic rhinitis (AR). Moreover, epidemiologic data on rhinitis in the elderly subjects and in southern Europe are scarce., Objective: This study aimed at estimating the prevalence and at comparing the risk factor distribution of AR and NAR in a general population sample aged 20-84 years in Italy., Methods: A questionnaire on respiratory symptoms and risk factors was administered to random samples of the Italian population aged 20-44 (n = 10,494) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Current AR and NAR were defined according to the self-reported presence of nasal allergies or of nasal symptoms without a cold or the flu., Results: NAR showed a significant descending pattern in females from 12.0 % (95 % CI 11.1, 13.1) in the 20-44 year age class, to 7.5 % (5.4, 10.3) in the 65-84 year age class (p = 0.0009), and a roughly stable pattern in males, from 10.2 % (9.3, 11.2) to 11.1 % (8.4, 13.9) (p = 0.5261). AR decreased from 26.6 % (25.7, 27.6) in 20-44 years age class to 15.6 % (13.3, 18.0) in the 65-84 years age class (p < 0.0001), without gender difference. Subjects living near industrial plants and ex- and current smokers had a higher risk of NAR. Current smokers had a lower risk and subjects living in a Mediterranean climate a higher risk of AR., Conclusion: AR and NAR are fairly distinct conditions, as they have a different age, gender and risk factor distribution.

Background: Studies on the prevalence of eczema and atopic dermatitis (AD), and on the factors associated with these diseases, have been mostly performed in children, whereas studies on adult populations are lacking., Objectives: To determine the prevalence of eczema and AD in the Italian adult population, and to investigate risk factors associated with the disease., Methods: A postal screening questionnaire was administered to 18 357 randomly selected subjects aged 20-44 years in the Gene-Environment Interaction in Respiratory Diseases study, which involved seven centres distributed across northern, central and southern Italy. The questionnaire included items on the occurrence of doctor-diagnosed eczema, asthma and hay fever, socio-demographic characteristics and environmental exposures., Results: In all, 10 464 (57.0%) subjects responded to the questionnaire. The prevalence of current eczema was 8.1% (95% CI: 7.6-8.7%), while the prevalence of eczema with asthma and/or hay fever (EAH), which was adopted as proxy of AD, was 3.4% (95% CI: 3.1-3.8%). About 60% of the subjects with current eczema reported the onset of the disease in adulthood. In multi-variable models, the prevalence of eczema was significantly associated with female sex, older age, living close to industrial plants, high levels of heavy traffic near home and living in central-southern Italy., Conclusions: Eczema and EAH are highly prevalent in Italian young adults, especially in women. Our results suggest that adult onset is not unusual, and that environmental factors may influence the occurrence of eczema and EAH., (© 2014 European Academy of Dermatology and Venereology.)