The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lung diseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and to prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model.

Commission VI, WG VI/4 KEY WORDS: HBIM, NURBS, PARAMETRIC MODEL, LOD, LOG, LOI, FEA, TOOLS, PRESERVATION ABSTRACT:In December 2012 ENIservizi (the Italian multi-national energy agency operating in many countries), after the Earthquake that occurred in April 2009, decided to undertake the project 'Re-start from Collemaggio' with the aim of giving new hope to the L'Aquila community, funding around 14 million Euro to restore the Basilica di Collemaggio. The Superintendence Office carried on the restoration project with the scientific support of the Università degli Studi de L'Aquila and the Università La Sapienza di Roma, under the coordination of the Politecnico di Milano. ENIservizi, aware of the BIM potential in the complex building and infrastructure domain in the world, required an advanced HBIM from the laser scanner and photogrammetric surveying to support the diagnostic analysis, the design project, the tender and the restoration itself, today still on course. Plans and vertical sections were delivered (2012) starting from the surveying campaigns (February and June 2013), together with the first HBIM advancement from the end of 2012 in support of the preliminary-definitive-executive steps of the restoration design project (2013-14-15). Five years later, this paper tries to make a synthesis of the different lessons learnt, in addition to the positive and critical aspects relating HBIM feasibility, sustainability and usefulness to the challenging restoration work. In particular, the Collemaggio BIM experience anticipated the new Italian Public Procurement Legislation (D.Lgs 50/2016, Nuovo Codice degli Appalti pubblici) aligned with to the EUPPD 24/2014: the EU Directive on Public Procurement asked all the 28 EU countries to adopt building informative modelling by February 2016 in order to support the whole LCM (Life Cycle Management), starting from the project and the intervention, through rewarding scores or mandatory regulations. Many analyses foresees to save from around 5% to 15% of the overall investment by adopting mature BIM (Level 3 to 5), particularly 4D remotely controlled BIM in support of the LCM, as in the case of maintenance and management process. The tender for Basilica restoration was published in 2015: the process was not developed enough to introduce selective criteria based on BIM adoption by the Construction Industry due to the lack of legislation at that time and the lack of BIM skills among the companies. Nevertheless ENIservizi also separately funded aside the HBIM of the Basilica to tackle an advanced BIM able to address decision-making processes in the heritage domain among the different actors: to support operators, architects, structural engineers, economic computation, construction site management and restoration, the theoretical and practical approach adopted by the HBIM, overcame the current logic based on sequential LoD (from simplex to complex, from the preliminary to the executive design) that is typical of new constructions in favour of a complex LoD approach that could guar...

Berylliosis is a granulomatous disorder of the lung caused by inhalation of beryllium (Be) and dominated by the accumulation of CD4+ T-helper (Th)1 memory T-cells proliferating in response to Be in the lower respiratory tract. Two gene markers have been associated with susceptibility to berylliosis: 1) the human leucocyte antigen (HLA)-DP gene whose allelic variants, carrying glutamate in position 69 of the β-chain (HLA-DPGlu69), can bind Be directly and present it to interferon (IFN)-γ releasing Th1 T-cell clones from patients with berylliosis; and 2) the cytokine gene tumour necrosis factor (TNF)-α which has been shown to increase berylliosis risk independent of HLA-DPGlu69.In order to determine whether TNF-α release was triggered by Th1 T-cell activation by Be stimulation in the context of HLA-DPGlu69 molecules, the proliferation of BeSO4-stimulated blood mononuclear cells and the release of IFN-γ, TNF-α, RANTES (regulated on activation normal T-cell expressed and secreted), granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4, IL-6, IL-8, IL-10 and IL-12 by BeSO4-stimulated blood mononuclear cells was quantified in 11 individuals with berylliosis using an anti-HLA-DP antibody as a probe for HLA-DP restricted T-cell activation.While proliferation and IFN-γ release were completely abrogated by HLA-DP inhibition (inhibition with anti-HLA-DP monoclonal antibody (mAb): 88±16 and 77±16%, respectively; anti-HLA-DR: 29±38 and 14±10%, respectively), the release of TNF-α was not (inhibition with anti-HLA-DP mAb: 8.9±7.8%). No other cytokine was detected at significant levels. Moreover, Be was able to induce TNF-α production in healthy control subjects not exposed to Be in the absence of T-cell proliferation and IFN-γ production.In conclusion, these data suggest that the tumour necrosis factor-α response of mononuclear cells is independent of the activation of beryllium-specific human leucocyte anitgen-DP restricted T-cells, which is consistent with the finding that the tumour necrosis factorA2 and the human leucocyte anitgen-DPGlu69 genetic markers are independently interacting in increasing berylliosis risk.

No abstract

No abstract