Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients

BACKGROUND: In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. METHODS: As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV(1 )94% of predicted) at three times over a three year period. RESULTS: There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV(1), MEF(75/25%VC), and MEF(25%VC). The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. CONCLUSION: Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease

Alterations in the human lung proteome with lipopolysaccharide

<p>Abstract</p> <p>Background</p> <p>Recombinant human activated protein C (rhAPC) is associated with improved survival in high-risk patients with severe sepsis; however, the effects of both lipopolysaccharide (LPS) and rhAPC on the bronchoalveolar lavage fluid (BALF) proteome are unknown.</p> <p>Methods</p> <p>Using differential in gel electrophoresis (DIGE) we identified changes in the BALF proteome from 10 healthy volunteers given intrapulmonary LPS in one lobe and saline in another lobe. Subjects were randomized to pretreatment with saline or rhAPC.</p> <p>Results</p> <p>An average of 255 protein spots were detected in each proteome. We found 31 spots corresponding to 8 proteins that displayed abundance increased or decreased at least 2-fold after LPS. Proteins that decreased after LPS included surfactant protein A, immunoglobulin J chain, fibrinogen-γ, α₁-antitrypsin, immunoglobulin, and α₂-HS-glycoprotein. Haptoglobin increased after LPS-treatment. Treatment with rhAPC was associated with a larger relative decrease in immunoglobulin J chain, fibrinogen-γ, α₁-antitrypsin, and α₂-HS-glycoprotein.</p> <p>Conclusion</p> <p>Intrapulmonary LPS was associated with specific protein changes suggesting that the lung response to LPS is more than just a loss of integrity in the alveolar epithelial barrier; however, pretreatment with rhAPC resulted in minor changes in relative BALF protein abundance consistent with its lack of affect in ALI and milder forms of sepsis.</p

Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

Cortical regional hyperperfusion in nonconvulsive status epilepticus measured by dynamic brain perfusion CT

BACKGROUND AND PURPOSE: Nonconvulsive status epilepticus (NCSE) is associated with a mortality rate of up to 18%, therefore requiring prompt diagnosis and treatment. Our aim was to evaluate the diagnostic value of perfusion CT (PCT) in the differential diagnosis of NCSE versus postictal states in patients presenting with persistent altered mental states after a preceding epileptic seizure. We hypothesized that regional cortical hyperperfusion can be measured by PCT in patients with NCSE, whereas it is not present in postictal states. MATERIALS AND METHODS: Nineteen patients with persistent altered mental status after a preceding epileptic seizure underwent PCT and electroencephalography (EEG). Patients were stratified as presenting with NCSE (n = 9) or a postictal state (n = 10) on the basis of clinical history and EEG data. Quantitative and visual analysis of the perfusion maps was performed. RESULTS: Patients during NCSE had significantly increased regional cerebral blood flow (P > .0001), increased regional cerebral blood volume (P > .001), and decreased (P > .001) mean transit time compared with the postictal state. Regional cortical hyperperfusion was depicted in 7/9 of patients with NCSE by ad hoc analysis of parametric perfusion maps during emergency conditions but was not a feature of postictal states. The areas of hyperperfusion were concordant with transient clinical symptoms and EEG topography in all cases. CONCLUSIONS: Visual analysis of perfusion maps detected regional hyperperfusion in NCSE with a sensitivity of 78%. The broad availability and short processing time of PCT in an emergency situation is a benefit compared with EEG. Consequently, the use of PCT in epilepsy may accelerate the diagnosis of NCSE. PCT may qualify as a complementary diagnostic tool to EEG in patients with persistent altered mental state after a preceding seizure

[Acute headache in a case of cerebral cavernomas]

We report a case of a 52-year-old female patient with known cerebral cavernomas and acute headache. A cranial CT scan excluded an intracranial bleeding. Cavernomas are rare vascular malformations of the venous blood system (synon. cavernous angiomas) with a slow blood flow. Clinical manifestation is presented between an age of 30-50 years with mostly unspecific neurological symptoms like headache, nausea, vomiting and dizziness, but also epileptic seizures and bleedings may occur. In general, therapy is symptomatic. In cases of seizures, however, anticonvulsive treatment is indicated. Operation can be discussed for peripheral localized cavernomas with bleeding or for refractory seizures. If antiplatelet or anticoagulation therapy is necessary due to other diseases (coronary heart disease, atrial fibrillation, thrombosis, pulmonary embolism), cerebral cavernomas are not considered as an absolute contraindication. The risk for an ischemic stroke under atrial fibrillation (5-20%), for example, is higher than the risk for bleeding of a cerebral cavernoma under anticoagulation therapy