Background: Despite the widespread use of fractional exhaled nitric oxide (FE NO ) as a biomarker of airways inflammation, there are no published papers describing normal FE NO values in a large group of healthy adults.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

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Key Points• In SCD, recurrent vasoocclusive crisis suppresses osteogenic lineage and activates osteoclasts.• Zoledronic acid acting on both osteoclast and osteoblast compartments is a multimodal therapy to prevent SBD.Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/ osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD. (Blood. 2015;126(20):2320-2328 IntroductionSickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75 000 individuals in the United States and almost 20 000 to 25 000 individuals in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharan Africa to European countries.1-3 Studies of the global burden of disease have pointed out the invalidating impact of SCD on patient quality of life.2 This requires the development of new therapeutic options to treat sickle cell-related acute and chronic complications.SCD is caused by a point mutation in the b-globin gene resulting in the synthesis of pathologic hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density, and further acceleration of HbS polymerization. [4][5][6] Pathophysiologic studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of ...

Twenty four workers (10 involved in the preparation and 14 in administration) exposed to cyclophosphamide (CP) and ifosfamide (IF) in two Italian hospitals were monitored. The extent of exposure was assessed by the analysis of air samples, wipe samples, pads and gloves. Urinary excretion at the beginning and at the end of the work shift was also measured by liquid-liquid extraction and analysis by high performance liquid chromatography/tandem mass spectrometry. Three out of 24 air samples were positive for CP or IF. In wipe samples, CP concentrations ranging from < 0.001 to 82.4 micrograms/dm2 in Hospital A (32 samples) and from 0.2 to 383.3 micrograms/dm2 in Hospital B (17 samples), were found. IF concentrations varied from < 0.001 to 90.9 micrograms/dm2 in Hospital A and from 0.01 to 141.5 micrograms/dm2 in Hospital B. Pads (from 11 to 13 for each operator) were contaminated with CP and IF especially on arms, legs and chest. The use of a plastic-backed liner on the working tray in the laminar flow hoods was demonstrated to compromise the containment properties of the hood. Urine samples were positive for CP in 50% of the workers (range: 0.1-2.1 micrograms/L), whereas IF was detected in 2 subjects only (range: 0.1-0.8 microgram/L). The results of this investigation demonstrate that vertical laminar airflow hoods, when incorrectly used, might represent a source of contamination and that higher risk may depend on lack of educational programmes and observance of preventive guidelines.