Metabolic phenotyping of human blood plasma: a powerful tool to discriminate between cancer types?

BACKGROUND: Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. However, up to now it is not clear whether different cancer types are characterized by a specific metabolite profile. Therefore, this study aims to evaluate whether the plasma metabolic phenotype allows to discriminate between lung and breast cancer. PATIENTS AND METHODS: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 80 female breast cancer patients and 54 female lung cancer patients, all with an adenocarcinoma. The validity of the model was examined by permutation testing and by classifying an independent validation cohort of 60 female breast cancer patients and 81 male lung cancer patients, all with an adenocarcinoma. RESULTS: The model allows to classify 99% of the breast cancer patients and 93% of the lung cancer patients correctly with an area under the curve (AUC) of 0.96 and can be validated in the independent cohort with a sensitivity of 89%, a specificity of 82% and an AUC of 0.94. Decreased levels of sphingomyelin and phosphatidylcholine (phospholipids with choline head group) and phospholipids with short, unsaturated fatty acid chains next to increased levels of phospholipids with long, saturated fatty acid chains seem to indicate that cell membranes of lung tumors are more rigid and less sensitive to lipid peroxidation. The other discriminating metabolites are pointing to a more pronounced response of the body to the Warburg effect for lung cancer. CONCLUSION: Metabolic phenotyping of plasma allows to discriminate between lung and breast cancer, indicating that the metabolite profile reflects more than a general cancer marker. CLINICAL TRIAL REGISTRATION NUMBER: NCT02362776.

The inner and outer of our thorax: silicone breast implants and pulmonary alveolar proteinosis.

Pulmonary alveolar (phospholipo)proteinosis (PAP) is a rare lung disease, predominantly autoimmune in nature. This case report describes a patient with insidious dyspnoea since 5 years and a milky appearance of her bronchoalveolar fluid, leading to the diagnosis of PAP. The onset of symptoms coincided with an exchange of her silicone breast implants. Giant cell reaction in axillary adenopathies pointed towards silicone leakage. Adjuvants, such as silicone, might boost pre-existing antigen reactions of the immune system, potentially leading to autoimmune phenomena.

Intermittent positive airway pressure by nasal mask as a treatment for respiratory insufficiency in a patient with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary neuropathy characterised by degeneration of motor and sensory peripheral nerves resulting in distal muscle weakness with atrophy and sensory impairment. We report a 35-year-old woman with CMT presenting with respiratory failure due to a pneumonia, sputum impaction and insufficient cough reflex. After recovery, we diagnosed a very severe restrictive lung function disturbance caused by muscle weakness and a possible coexistent unilateral diaphragm paralysis. A very severe REM (Rapid Eye Movement Sleep) related sleep hypopnea syndrome was successfully treated with Nasal Intermittent Positive Pressure Ventilation (NIPPV).

Role of N-acetylcysteine in the management of COPD.

The importance of the underlying local and systemic oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD) has long been established. In view of the lack of therapy that might inhibit the progress of the disease, there is an urgent need for a successful therapeutic approach that, through affecting the pathological processes, will influence the subsequent issues in COPD management such as lung function, airway clearance, dyspnoea, exacerbation, and quality of life. N-acetylcysteine (NAC) is a mucolytic and antioxidant drug that may also influence several inflammatory pathways. It provides the sulfhydryl groups and acts both as a precursor of reduced glutathione and as a direct reactive oxygen species (ROS) scavenger, hence regulating the redox status in the cells. The changed redox status may, in turn, influence the inflammation-controlling pathways. Moreover, as a mucolytic drug, it may, by means of decreasing viscosity of the sputum, clean the bronchi leading to a decrease in dyspnoea and improved lung function. Nevertheless, as successful as it is in the in vitro studies and in vivo studies with high dosage, its actions at the dosages used in COPD management are debatable. It seems to influence exacerbation rate and limit the number of hospitalization days, however, with little or no influence on the lung function parameters. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives with their multiple molecular modes of action remain promising medication once doses and route of administration are optimized.