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Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12–120months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1>12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre-/post-treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p=0.0001, 81.8% [66.1–94.3], p=0.0001, 21[18–23], p=0.045 and 230 cells/µl [80–360], p=0.003). A negative relationship between SABA-induced FEV1% changes and pre-bronchodilator FEV1% (β=−0.551%; p=0.0001) and ACT (β=−0.059; p=0.038) was found. Conversely, post-treatment BE levels were positively related (β=145.565 cells/µl; p=0.003) to FEV1>12% increases. A rising trend of pre-/post-bronchodilator FEV1% in time was observed in RAO− subjects with BE300 cells/µl reaching lower values after more than 36months of step-5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE300 cells/µl [p=0.009]). Conclusion: Persistent SABA-induced FEV1>12%, especially when associated to BE>300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.

Several severe asthma comorbidities have been identified: an emerging one is bronchiectasis. We evaluated the frequency of bronchiectasis on severe asthma in a real-life setting, through the 'Severe Asthma Network Italy' (SANI) registry.SANI registry encompasses demographic, clinical, functional and inflammatory data of Italian severe asthmatics. Data obtained by the enrolled patients were analyzed, focusing the attention on those patients with concomitant clinically relevant bronchiectasis.About 15.5% patients have bronchiectasis. Bronchiectasis diagnosis was associated with a higher prevalence of chronic rhinosinusitis with nasal polyps (54.6% vs. 38%, p = 0.001) and higher serum IgE levels (673.4 vs. 412.1 kUI/L, p = 0.013). Patients with bronchiectasis had worse asthma control (ACT: 16.7 vs 18.2, p = 0.013), worse quality of life (AQLQ: 4.08 vs. 4.60, p = 0.02) and lower lung function (FEVsevere asthma associated with bronchiectasis represents a particularly severe asthma variant, possibly driven by an eosinophilic endotype. We, therefore, suggest that bronchiectasis should necessarily be assessed in severe asthmatic patients.

Recently, dupilumab, an anti-IL-4Rα antibody, has become available for the treatment of moderate-to-severe atopic dermatitis (AD).1-4 Baseline patient characteristics that can be used as predictors of response to dupilumab treatment in AD patients have not yet been identified.

Background Moderate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD. Objectives A multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from >= 12 to

Background The clinical and laboratory features of patients enrolled in the Severe Asthma Network in Italy (SANI) registry, a web-based observatory collecting demographic, clinical, functional and inflammatory data of patients with severe asthma were evaluated, with a special emphasis to chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods For each eligible patients the following information has been collected: demographic data, clinical features, asthma control in the previous month according to the GINA (Global INitiative for Asthma) Guidelines and standardized questionnaires, concomitant regular and on demand treatments and inflammatory markers. Results 695 patients with severe asthma enrolled in 66 SANI centers were analyzed. The prevalence of chronic rhinosinusitis with nasal polyposis was 40.6%. Atopic dermatitis and bronchiectasis was significantly more frequent in patients with CRSwNP than in subjects without nasal polyposis; similarly, FeNO values are significantly higher in subject with CRSwNP than in patients without nasal polyposis. Finally, patients with CRSwNP had a significantly higher number of asthma exacerbations per year, more days on oral corticosteroids and were more likely to be OCS long term users. Conclusion OCS sparing is needed in patients with severe asthma, mainly in subjects with CRSwNP, adopting adequate strategies such as a better adherence to the treatment with inhaled therapy according to the GINA recommendations, the use of biologic agents and a multidisciplinary approach of the patient.

Objective: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. Methods: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures includedthe mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. Results: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. Conclusions: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

To the Editor Since the end of February 2020 Italy, first non- Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200,000 confirmed Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infected subjects and resulted in more than 34000 deaths (data updated to June 19th, 20201).Patients with asthma are potentially more severely affected by by SARS-CoV-2 infection 2 and it is well established that respiratory viral infections are associated with severe adverse outcomes in patients with asthma, including increased risk of asthma exacerbation episodes 3. Nonetheless, according to the epidemiological studies published so far, chronic pulmonary diseases are not amongst the most common clinical conditions in COVID-19 patients4About 5-10% of entire asthma population, are severe asthmatics5 and one would expect increased vulnerability to SARS-CoV-2 infection, but no data is so fare available ti confirm this hypothesis.We investigated the incidence of COVID-19, describing its clinical course, in the population of the Severe Asthma Network in Italy (SANI), one of the largest registry for severe asthma worldwide6, and in an additional Center (Azienda Ospedaliero Univeristaria di Ferrara, Ferrara, Italy). All centers, have been contacted and inquired to report confirmed (i.e. patients with positive test result for the virus SARS-CoV-2 from analysis of nasopharyngeal or oropharyngeal swab specimens) or highly suspect cases of COVID-19 (i.e. patients with symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. Demographic and clinical data of the entire cohort of severe asthmatics enrolled in the study and all reported cases of confirmed or suspect cases of COVID-19, have been obtained from the registry platform and collected from the additional Center. Additional data about COVID-19 symptoms, treatment and clinical course have been collected for all cases reported.Ethical issues and statistical analysis are reported in the online supplementary material.Twenty-six (1.73%) out of 1504 severe asthmatics had confirmed (11 out of 26) or highly suspect COVID-19 (15 out 26); eighteen (69.2%) were females and mean age was 56.2 ± 10 years. The geographical distribution of COVID-19 cases is presented in Figure 1.Nine (34.6%) infected patients experienced worsening of asthma during the COVID-19 symptomatic period; four of them needed a short course of oral corticosteroids for controlling asthma exacerbation symptoms.The most frequent COVID-19 symptoms reported were fever (100% of patients), malaise (84.6%), cough (80.8%), dyspnea (80.8%), headache (42.3%) and loss of smell (42.3%). Four patients (15.3%) have been hospitalized, one of which in intensive care unit; among hospitalized patients, two (7.7%) died for COVID-19 interstitial pneumonia. No deaths have been reported among the non-hospitalized patients.Severe asthmatics affected by COVID-19, had a significantly higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) compared to non-infected severe asthma patients (15.4% vs 3.8%, p=0.002; odds ratio: 4.7). No difference was found in other comorbidities (including rhinitis, chronic rhinosinusitis with or without nasal polyps, bronchiectasis, obesity, gastroesophageal reflux, arterial hypertension, cardiovascular diseases).Twenty-one patients with COVID-19 were on biological treatments: 15 (71%) were on anti-IL-5 or anti-IL5R agents (Mepolizumab n= 13; Benralizumab n=2 - counting for the 2.9% of all severe asthmatics treated with anti-IL5 in our study population) and 6 (29%) were on anti IgE (Omalizumab - 1.3% of all severe asthmatics treated with omalizumab in our study population).Table I summarizes demographic and clinical characteristics of the 26 COVID-19 patients.In conclusion, in our large cohort of severe asthmatics, COVID-19 was infrequent, not supporting the concept of asthma as a particularly susceptible condition to SARS-COV2 infection 2. This is in line with the first published large epidemiological data on COVID-19 patients, in which asthma is under-reported as comorbidity4. The COVID-19 related mortality rate in our cohort of patients was 7.7%, lower than the COVID-19 mortality rate in the general population (14.5% in Italy 1). These findings suggest that severe asthmatics are not at high risk of the SARS-CoV-2 infection and of severe forms of COVID-19. There are potentially different reasons for this. Self-containment is the first, because of the awareness of virus infections acting as a trigger for exacerbations, and therefore they could have acted with greater caution, scrupulously respecting social distancing, lockdown and hygiene rules of prevention, and being more careful in regularly taking asthma medications.Another possible explanation stands in the intrinsic features of type-2 inflammation, that characterizes a great proportion of severe asthmatics. Respiratory allergies and controlled allergen exposures are associated with significant reduction in angiotensin-converting enzyme 2 (ACE2) expression 7, the cellular receptor for SARS-CoV-2. Interestingly, ACE2 and Transmembrane Serine Protease 2 (TMPRSS2) (another protein mediating SARS-CoV-2 cell entry) have been found highly expressed in asthmatics with concomitant NIDDM8, the only comorbidity that was more frequent reported in our COVID-19 severe asthmatics.The third possible explanation refers to the possibility that inhaled corticosteroids (ICS) might prevent or mitigate the development of Coronaviruses infections. By definition, patients with severe asthma are treated with high doses of ICS 5 and this may have had a protective effect for SARS-CoV-2 infection.Noteworthy, among the patients of our case-series of severe asthmatics with COVID-19, the proportion of those treated anti-IL5 biologics was higher (71%) compared to the number of patients treated with anti-IgE (29%). Although the number of cases is too small to draw any conclusion, it is tempting to speculate that different biological treatments can have specific and different impact on antiviral immune response. In addition we may speculate of the consequence of blood eosinophils reduction: eosinopenia has been reported in 52-90% of COVID-19 patients worldwide and it has been suggested as a risk factor for more severe COVID-19 9.In conclusion, in our large cohort of severe asthmatics only a small minority experienced symptoms consistent with COVID-19, and these patients had peculiar clinical features including high prevalence of NIDDM as comorbidity. Further real-life registry-based studies are needed to confirm our findings and to extend the evidence that severe asthmatics are at low risk of developing COVID-19.

Background: Treatment of moderate-to-severe atopic dermatitis (AD) in the elderly may be challenging, due to side-effects of traditional anti-inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known. Objectives: A multicentre retrospective, observational, real-life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65years and affected by severe AD. Their main clinical features were also examined. Methods: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16weeks of treatment. Results: Two hundred and seventy-six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16-week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18–64years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty-one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event. Conclusions: Therapy with dupilumab led to a significant improvement of AD over a 16-week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.

The questions of whether high-income individuals are more prosocial than low-income individuals and whether income inequality moderates this effect have received extensive attention. We shed new light on this topic by analyzing a large-scale dataset with a representative sample of respondents from 133 countries ( N = 948,837). We conduct a multiverse analysis with 30 statistical models: 15 models predicting the likelihood of donating money to charity and 15 models predicting the likelihood of volunteering time to an organization. Across all model specifications, high-income individuals were more likely to donate their money and volunteer their time than low-income individuals. High-income individuals were more likely to engage in prosocial behavior under high (vs. low) income inequality. Avenues for future research and potential mechanisms are discussed.

Background: It is important to identify patients with monogenic IBD since management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups. Methods: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists). Results: We recommend next-generation DNA sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD onset (infantile IBD, very early onset IBD, paediatric or young adult IBD) and further criteria such as family history, relevant comorbidities and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We develop a diagnostic algorithm that includes a gene panel of seventy-five monogenic IBD genes. Considerations are provided also for low resource countries. Summary: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD.

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.

Tesi sostenuta La questione ambientale dal punto di vista delle città è questione urbana. Le città si possono considerare come dei veri e propri ecosistemi complessi che interagiscono con una miriade di questioni ambientali dalla produzione/consumo del cibo, all’energia, ai rifiuti e all’inquinamento, come sfide sociali in materia di lavoro, povertà e benessere. Lo strumento chiave, per il conseguimento degli obiettivi di sviluppo sostenibile, è sicuramente rappresentato dall’incorporazione/sintesi di conoscenze e principi di ecologia nella gestione del territorio antropizzato al fine di sviluppare ecosistemi urbani sani, vivibili, sostenibili e resilienti. Per tale motivo le città devono essere considerate come dei veri e propri ecosistemi complessi che vanno difesi attraverso la conoscenza degli equilibri e delle condizioni ambientali con lo scopo fondamentale di garantire la crescita e la riproduzione delle diverse specie. Principali argomentazioni Gli ecologi, per oltre un secolo, hanno analizzato i sistemi naturali trascurando le aree edificate/antropizzate. Gli aggettivi urbano ed ecologico per molti studiosi sono considerati in antitesi [McIntyre et al, 2000] e hanno preferito studiare la natura senza l’uomo [Collinset al, 2000; Wu & Loucks, 1995]. Dei circa 6.000 articoli scientifici pubblicati in nove principali riviste di ecologia, nel periodo 1995-2000, solo 25 e cioè lo 0,2% hanno trattato argomenti relativi alle città [Benton-Short and Short, 2008]. La Pianificazione urbanistica italiana, è articolata attraverso un complesso e rigido sistema gerarchico, in base al quale le previsioni del livello sovra-ordinato ingabbiano le scelte di quello sotto-ordinato. Inoltre, con il DLgs n.152/2006 smi l’Italia ha recepito la Direttiva 42/2001/CE rendendo obbligatoria la VAS, che subordina l’operatività dei Piani alla compatibilità ambientale accentuando ulteriormente la rigidità del modello tradizionale di Pianificazione. Tale sistema è caratterizzato da un grado assai basso di efficacia e necessita di un profondo ripensamento. Le nuove sfide per la Pianificazione riguardano pertanto il raggiungimento dell’adattabilità del Territorio antropizzato ai cambiamenti in atto, in modo particolare a quelli ambientali. Contribuire alla comprensione delle complesse questioni ambientali interagenti con la Pianificazione del Territorio, attraverso analisi inter-settoriali e inter-disciplinari consente di individuare nuove categorie interpretative e descrittive finalizzate all’analisi e al progetto dello spazio fisico contemporaneo. Metodologia/Caso di Studio/Comparazioni, etc. Domini della ricerca: Literature review e Theory in Relation to Method. Strategia della ricerca: Combined strategies [Groat & Wang 2002/2013]. Esiti attesi Il paper propone alcune riflessioni e spunti al dibattito nell’intento di contribuire all’aggiornamento e adeguamento delle discipline del piano tradizionali alle complesse ed emergenti questioni ambientali, attraverso l’individuazione dei contenuti essenziali di nuovi apparati conoscitivi e strumenti tecnico-scientifici di pianificazione che siano in grado di superare la gerarchizzazione e la settorialità dei piani verso l’Eco-Planning.

Francesca Puggioni,1,2 Luisa Brussino,3 Giorgio Walter Canonica,1,2 Francesco Blasi,4,5 Pierluigi Paggiaro,6 Marco Caminati,7,8 Manuela Latorre,6 Enrico Heffler,1,2 Gianenrico Senna7,8 On behalf of the Severe Asthma Network in Italy (SANI) group1Personalized Medicine, Asthma and Allergy – Humanitas Clinical and Research Center, IRCCS – Rozzano (MI), Milan, Italy; 2Department of Biomedical Sciences, Humanitas University – Pieve Emanuele (MI), Milan, Italy; 3Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I – Torino, Torino, Italy; 4Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 5Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy; 6Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy; 7Department of Medicine, University of Verona, Verona, Italy; 8Allergy Unit and Asthma Center, Verona University Hospital, Verona, Verona, ItalyCorrespondence: Enrico HefflerPersonalized Medicine, Asthma and Allergy, Istituto Clinico Humanitas, Milan, ItalyTel +39 0288247013Fax + 39 0282246484Email enrico.heffler@hunimed.euPurpose: Patients with uncontrolled asthma despite high doses of inhaled corticosteroid therapy plus another controller are defined as severe asthmatics. Tiotropium bromide respimat (TBR) is the only long-acting muscarinic antagonists (LAMA) approved for severe asthma. The aim of this study was to explore the frequency of severe asthmatics treated with TBR and characterize their clinical features in a real-life, registry-based setting.Materials and Methods: Baseline data from the Severe Asthma Network in Italy (SANI) registry have been analyzed to determine the use of TBR and other LAMA, and to compare clinical, functional and inflammatory features associated with the use of LAMA.Results: Among a total of 698 enrolled patients, 35.9% were treated with LAMA (23.3% TBR, 4.5% tiotropium bromide handihaler, 4.5% aclidinium, 3.4% glycopyrronium bromide 0.3% umeclidinium bromide). Age of asthma onset was higher in patients taking LAMA, whom, compared to others were more frequently former smokers. They also had a higher annual exacerbation rate, experienced worst asthma control, worst disease-related quality of life and poorer lung function. Bronchiectasis was more frequently found in LAMA users (25.9% vs 13.1%).Conclusion: TBR is still underused in severe asthma in a real-life setting, while a relevant proportion of patients are treated with other LAMA that are not approved for severe asthma treatment. Patients taking LAMA have features characteristic of even more severe asthma.Keywords: severe asthma, registry, long-acting muscarinic antagonists, real-ligfe

The western economic model that took shape beginning in the industrial revolution has produced important changes in the equilibrium of ecosystems along with large-scale environmental transformation. The most common industrial processes consume materials and energy to manufacture goods and services generating a considerable amount of waste. This might be environmentally sustainable if resources were inexhaustible and space unlimited. The emissions of pollutants into the air and water, deforestation, desertification of vast regions and coastal erosion, as well as urban and infrastructural development are causes of global threats even on the urban planning scale. As a result of these circumstances, urban and regional planning saw an epistemological revision with the development of environmental planning; in other words, the environmental dimension became a factor in urban and regional planning. The topic of the environmental improvement of industrial zones is relatively new on the international scene (Fieldbook for the development of Eco-Industrial Parks, Lowe, Moran and Holmes, 1996). Only since the early 1990s in the United States, as well as in Asia and Europe, have voluntary experiments been undertaken to create industrial zones with reduced environmental impacts. The paper seeks to identify some environmental criteria that characterize eco-industrial settlements on the urban scale, which might be a more appropriate one for the correct recovery of existing areas and the design of new ones.

Purpose After adolescence, asthma is more frequent in females than in males due to different hormonal, immunologic, and occupational/environmental factors. The higher prevalence and severity of the disease in females have already been reported in international registries. The aim of this study was to explore the difference in terms of clinical, functional, and biological characteristics between male and female patients with severe asthma in a real-life, registry-based setting. Methods Baseline data from the Severe Asthma Network in Italy registry were analyzed in 1,123 patients with severe asthma, according to sex. Results Almost 2/3 of severe asthmatics were female. Late-onset asthma, obesity and gastro-esophageal reflux were more frequent in females than in males, while previous smoking habits and nasal polyposis were more frequent in males. Females had poor asthma control and a higher number of severe exacerbations leading to hospitalization, in comparison to males. Biomarkers of type 2 inflammation (blood eosinophil, exhaled nitric oxide, and serum immunoglobulin E levels) were significantly higher in males than in females. The type 2 profile (defined by a combination of these 3 biomarkers) was significantly more frequent in males than in females. In multivariate analysis, late-onset asthma and a normal body mass index were only independent variables associated with the type 2 profile, while male sex and age showed only a trend toward the association with the type 2 profile. Conclusions Significant differences may be observed between male and female patients with severe asthma, influencing the asthma pheno-endotyping in both sexes.

Negli ultimi cinquantanni, eventi sismici di magnitudo Richter superiori a cinque, hanno cancellato interi paesi italiani nella Valle del Belice (1968, magnitudo 5,9), nella Valle del Tagliamento (1976, magnitudo 6,5), in Irpinia (1980, magnitudo 6,9), in Umbria (1997, magnitudo 6,1/6,9), in Abruzzo (2009, magnitudo 6,3/5,8) e in Emilia (2012, magnitudo 5,6/5,8). I criteri utilizzati per l'analisi e la valutazione della vulnerabilità sismica di un insediamento sono solo di tipo edilizio (Dipartimento della Protezione Civile - Gruppo Nazionale per la Difesa dai Terremoti DPC-GNDT) e non interpretano la città come un sistema complesso di spazi adattati. La semplificazione, posta a base di tale modello, presuppone una città come banale somma dei suoi elementi edilizi, ma la città è un complesso sistema in cui le relazioni tra i vari componenti assumono un significato altrettanto importante. Il metodo della Struttura Urbana Minima (SUM) è finalizzato all’analisi e valutazione della vulnerabilità dei sistemi funzionali, insediativi e infrastrutturali, al verificarsi di un evento sismico, in una prospettiva temporale estesa che tenga conto, oltre che del danno immediato, degli effetti differiti e di lungo periodo. Il paper si propone di comparare l’indice di vulnerabilità sismica, ottenuto dall’applicazione di due metodi (DPC-GNDT e SUM), alla nuova Conza della Campania (Av) interamente ricostruita fuori sito, dopo il terremoto del 1980. Il contributo evidenzierà potenzialità e limiti dei due metodi e il ruolo che può essere attribuito alla pianificazione urbanistica degli insediamenti in zona sismica.

La pianificazione, progettazione e qualificazione ambientale degli insediamenti produttivi è un tema relativamente nuovo: solo a partire dagli anni ‘90 si sono diffuse esperienze volte a programmare un insediamento produttivo con un minore impatto sull'ambiente. Gli Eco-Industrial Park (EIP), teorizzati da Lowe, Moran e Holmes, nel testo Fieldbook for the development of Eco-Industrial Parks (1996), sono comunità di imprese manifatturiere e di servizio che cercano di migliorare la loro sostenibilità implementando le performance ambientali, economiche e sociali. Il percorso per raggiungere tale obiettivo ricorre alla pianificazione-progettazione dell’area produttiva sia attraverso un nuovo disegno sia con la riqualificazione delle infrastrutture esistenti (Lowe, 2003). Il raggiungimento dello status di EIP, necessita tanto di un coordinato processo di pianificazione a scala urbanistica ed edilizia, quanto dell’organizzazione della singola impresa. Il presente contributo cerca di approfondire, in particolare, l’aspetto della pianificazione urbanistica con l’intento di individuare alcuni primi criteri generali di Eco-Planning che caratterizzano questi insediamenti distinguendoli dalle condizioni di contesto. Tali primi criteri o invarianti potrebbero contribuire alla redazione di linee di indirizzo a supporto anche delle norme tecniche di attuazione degli strumenti urbanistici, generali e/o attuativi, più focalizzati sugli aspetti ambientali con l’obiettivo di migliorare la sostenibilità della realizzazione e/o riqualificazione delle aree produttive tanto in attuazione diretta che indiretta delle previsioni di piano.

Rural territory has not to be considered as an empty space to anthropize, but as a system combined to the city, since it is the place where basic processes of primary production, of biodiversity safeguard and of landscapes take place. Urban Planning has proved unable to conceive open spaces also because of the seeming indifference of such places towards building uses typical of urban regulations. By isolating problems of intervention to business interests, in its turn, agricultural planning has been unable to do better. Evaluations on agricultural areas cannot exhaust themselves in the scope of a general rule of production use or of environmental protection, but the role of an agricultural space as a heritage of the metropolis has to be recognized. This role cannot be neither entrusted to the individual interests of the private independent farmer, nor can it be only linked to the regulating ability of economics. It must be set among the targets of the higher public interest pursued by the physical territorial planning also in its contemporary version of eco-planning. Contemporary Urban Planning should begin looking at modern agriculture as a reality to establish new strategic relations with, according to a non-deterministic approach for the evolution of the urban environment. The integration of agricultural areas in the urban scope is a subject of great interest with a view to change our cities in environmentally more liveable places. In the scope of the debate on sustainable development, one of the central topics is the issue of marginal territories, in particular, the redefinition of reciprocity relations between agricultural territories and cities, between environmental systems and urban systems. The city has excessively spread, leaving neighbouring protected and agricultural areas as a reserve for urban growth. The whole XXth century has been characterized by a clear separation between agriculture and city. Some recent experiences show how a possible rebalance of the urban ecosystem can take place through the hybridization of the two systems, whose planning is one of the challenges of environmental planning. Urban, technological, landscape and environmental aspects coexist in it. Hence, a culture of plan and of project, renovating its reference models facing the challenge of a liquid modernity, establishing new relations with a culture other than agriculture, that is not a building culture under traditional terms, but is productive under enzymatic terms, that follows bio-compatible logics and uses highly advanced support technologies.

Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between poorly controlled and partially or well controlled asthmatics showed a statistically significant higher prevalence of some comorbidities in the first group, namely obesity, gastro-oesophageal reflux disease (GORD), aspirin intolerance and mental disorders (all p