Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified Timothy grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12) in patients undergoing hyposensitization treatment

ABSTRACTBackgroundThe diagnosis of allergic diseases with recombinant allergens allows us to detect antibodies specific for single allergens in extracts. The aim of the present study was to assess the early effect of grass pollen immunotherapy on IgE and IgG4 responses to eight purified grass pollen allergens in patients undergoing hyposensitization treatment.MethodsThe sera of 22 consecutive atopic individuals undergoing cluster regimen grass pollen immunotherapy were analyzed for IgE and IgG4 antibodies specific for grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12). Two serum samples were taken, one before the start of therapy and one between 12 and 15 weeks after the first immunization. Immunotherapy was performed with two allergy vaccines comprising a standardized extract aluminum-adsorbed grass pollen mix and a standardized extract of grass pollen mix adsorbed onto calcium phosphate.ResultsOne treated patient showed a specific IgE conversion from negative (<0.35 kUA/L) to positive in the capsulated hydrophilic carrier polymer (CAP) test for Phl p 2, 1 and 4 (1.89, 0.84 and 0.68 kUA/L, respectively). The sera of 10 of 11 patients treated with alluminum-adsorbed grass pollen extract showed a significant increase in specific IgG4 towards natural Timothy grass pollen extract and purified allergens, as well as significant IgG4 levels towards Phl p 1 (P = 0.000238) Phl p 2 (P = 0.000289), Phl p 4 (P = 0.000585), Phl p 5 (P = 0.000364), Phl p 6 (P = 0.000346) and Phl p 11 (P = 0.039623; Mann–Whitney U-test) 12 weeks after the onset of immunotherapy. The sera of seven of 11 subjects treated with calcium phospate-adsorbed grass pollen extract had significant IgG4 levels against Timothy pollen allergens, as well as significant IgG4 titers against Phl p 1 (P = 0.004703), Phl p 4 (P = 0.000282), Phl p 5 (P = 0.015480), Phl p 6 (P = 0.013012) and Phl p 11 (P = 0.005178). Patients treated with aluminum-adsorbed grass pollen extract had higher levels of IgG4 towards Phl p 2, 4 and 6 and natural Timothy grass extract compared with patients treated with calcium phosphate-adsorbed grass pollen extract. Both the alluminum-adsorbed and calcium phosphate-adsorbed grass pollen extract allergy vaccines induced significant titers of specific IgG4 towards Phleum pratense pollen extract (P = 0.008376 and 0.01148, respectively).ConclusionsThese results indicate that grass pollen immunotherapy elicits an array of antibody specificities that reflect the allergen content and the potency of allergen extracts; this could be of pivotal importance to define optimal allergen extract doses

Collaborative mapping response to disasters through OpenStreetMap: the case of the 2016 Italian earthquake

Digital humanitarians represent the current generation of volunteers providing timely contributions in the form of digital map data in the aftermath of natural disasters. Starting from the tragic 2010 earthquake in Haiti and thanks to the success of the OpenStreetMap (OSM) project, the presence and coordination of these volunteers have grown incredibly over the past years. This work investigates the dynamics of the mapping process and the nature of the OSM volunteers who contributed map data after the 2016 earthquake in Central Italy. The analyses show that the existing OSM users were the majority of those contributing to the mapping activity, with less edits performed by new users. The collaborative mapping process was efficiently coordinated through a dedicated platform and the area hit by the earthquake was significantly edited in OSM after the disaster

Phenotyping COVID-19 respiratory failure in spontaneously breathing patients with AI on lung CT-scan.

BACKGROUND: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes. METHODS: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7&nbsp;days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories. RESULTS: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar-hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables. CONCLUSIONS: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model

International audienceRespiratory diseases in Italy already now represent an emergency (they are the 3 rd ranking cause of death in the world, and the 2 nd if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine -again addressing the general population but aimed at measuring the individual's risk for disease insurgence; 2) actions of early diagnosis targeted at groups or -more precisely -subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support -destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document "Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)" of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document – produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise –after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,'case-finding'approach; (Continued on next page

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P&lt;0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)