Itraconazole as 'bridge therapy' to anti-IgE in a patient with severe asthma with fungal sensitisation.

Sensitisation to fungi has been reported to play an important role in a particular phenotype of severe asthma, the so-called severe asthma with fungal sensitisation, characterised by high levels of total IgE, which may be an obstacle to anti-IgE therapy. We describe here the case of a polysensitised woman with refractory asthma, sensitised to Aspergillus fumigatus with high total IgE values (1793 kUA/l), but without the diagnostic criteria for allergic bronchopulmonary aspergillosis. Additional therapy with itraconazole leads to the decrease of total IgE to the limits recommended for proper omalizumab dosing (30–1500 kUA/l). Itraconazole, used as bridge therapy, provided us the opportunity to start anti-IgE treatment in a patient with high levels of total IgE, beyond the upper limits recommended for proper prescription of omalizumab

Exhaled breath condensate nitrates, but not nitrites or FENO, relate to asthma control.

SummaryBackgroundAsthma is a chronic respiratory disease, characterised by airways inflammation, obstruction and hyperresponsiveness. Asthma control is the goal of asthma treatment, but many patients have sub-optimal control. Exhaled NO and exhaled breath condensate (EBC) NO metabolites (nitrites and nitrates) measurements are non-invasive tools to assess airways inflammation. Our aim was to investigate the relationships between asthma control and the above-named biomarkers of airways inflammation.MethodsThirty-nine non-smoking asthmatic patients (19 women) aged 50 (21–80) years performed measurements of exhaled NO (FENO), EBC nitrates, nitrites and pH, and answered Asthma Control Questionnaire (ACQ) and Asthma Control Test (ACT)-questionnaire.ResultsThe ACT and ACQ score were strongly interrelated (ρ=−0.84, p<0.001). No relationships between ACT or ACQ score and FENO were found (p>0.05). EBC nitrates were negatively related to ACT score (ρ=−0.34, p=0.03) and positively related to ACQ score (ρ=0.41, p=0.001) while no relation of EBC nitrites to either ACQ or ACT score was found (p>0.05).ConclusionEBC nitrates were the only biomarker that was significantly related to asthma control. This suggests that nitrates, but not nitrites or FENO, reflect an aspect of airways inflammation that is closer related to asthma symptoms. Therefore there is a potential role for EBC nitrates in objective assessment of asthma control

Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products

In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations

Dysphagia: An unusual presentation of giant aneurysm of the right coronary artery and supravalvular aortic stenosis in Williams syndrome

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