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CF Airway (cf + airway)
Selected AbstractsRelationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 4 2009Scott D. Sagel MD Abstract Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF-related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein-specific levels and airway inflammation and infection. Pediatr Pulmonol. 2009; 44:402,409. © 2009 Wiley-Liss, Inc. [source] Quantitative cytokine gene expression in CF airway,PEDIATRIC PULMONOLOGY, Issue 5 2004Marianne S. Muhlebach MD Abstract Bronchoalveolar lavage fluid (BALF) in cystic fibrosis (CF) shows increased inflammation, which could be due to abnormal cytokine regulation. Bronchial epithelial cells and migratory inflammatory cells produce these cytokines, but few quantitative in vivo data are available comparing young CF patients with controls. We hypothesized that IL-8 mRNA abundance was higher in young CF vs. non-CF disease control patients in lung epithelium and inflammatory cells. Bronchial epithelial cells (BEC) were obtained by brush biopsy, and airway inflammatory cells (BALFC) by bronchoalveolar lavage, in 17 CF and 21 non-CF patients <5 years old undergoing clinically indicated bronchoscopy. Cellular mRNA expression was quantified by real-time PCR and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Abundance of IL-8/GAPDH in BEC was significantly higher in CF (14.8,±,3.3) than non-CF (4.2,±,0.6) samples, and this difference was also significant when patients were stratified according to infection. In BALFC, the difference in IL-8 expression did not reach statistical significance: CF (17.1,±,6.5) vs. non-CF (6.8,±,1.9), but BALF cell number/ml was significantly higher in CF. IL-10 mRNA was very low in all samples, without showing a decrease in CF vs. non-CF patients. We conclude that early in the disease, IL-8 mRNA expression in BEC is increased in CF in vivo. Although IL-8 mRNA in migratory cells was not significantly higher in CF, these cells may still contribute to elevated IL-8 in airway secretions, secondary to increased cell density in BALF. Pediatr Pulmonol. 2004; 37:393,399. © 2004 Wiely-Liss, Inc. [source] Bone marrow stem cells do not repopulate the healthy upper respiratory tract,PEDIATRIC PULMONOLOGY, Issue 4 2002Jane C. Davies MD Abstract Recent studies reported differentiation of both bone marrow and tissue-specific stem cells into cells of other organs. The demonstration that bone marrow stem cells differentiate into human hepatocytes in vivo has raised the possibility of new therapeutic approaches for liver disease. For diseases such as cystic fibrosis (CF), correction of the respiratory epithelium is being attempted by gene therapy. Differentiation of bone marrow stem cells into epithelium of the lung and airway was recently reported in an animal model, and would provide an alternative approach. We examined the nasal epithelium of female patients up to 15 years after gender-mismatched bone marrow transplantation. Donor-derived epithelial cells were sought with a combination of Y-chromosome fluorescence in situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from 6 transplant-recipients, a median of 2.5% (range, 0.7,18.1%) of nuclei was male and identified as being of donor-origin. However, a complete absence of staining with anti-cytokeratin antibodies confirmed that these were not epithelial cells, but were likely to be either intraepithelial lymphocytes or mesenchymal cells. Following whole bone marrow transplantation, bone marrow progenitor cells do not differentiate into respiratory epithelium of the healthy upper airway. The differences between this and other studies could relate to the cells transplanted, to differential rates of turnover, or to the requirement for specific triggers to stimulate migration and differentiation. In the absence of such conditions, whole bone marrow transplantation is unlikely to provide a route for correction of the CF airway. Pediatr Pulmonol. 2002; 34:251,256. © 2002 Wiley-Liss, Inc. [source] Pharmacotherapy Of The Ion Transport Defect In Cystic FibrosisCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001Karl Kunzelmann SUMMARY 1. More than 1300 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF), a disease characterized by deficient epithelial Cl, secretion and enhanced Na+ absorption. The clinical course of the disease is determined by the progressive lung disease. Thus, novel approaches in pharmacotherapy are based primarily on correction of the ion transport defect in the airways. 2. The current therapeutic strategies try to counteract the deficiency in Cl, secretion and the enhanced Na+ absorption. A number of compounds have been identified, such as genistein and xanthine derivatives, which directly activate mutant CFTR. Other compounds may activate alternative Ca2+ -activated Cl, channels or basolateral K+ channels, which supply the driving force for Cl, secretion. Apart from that, Na+ channel blockers, such as phenamil and benzamil, are being explored, which counteract the hyperabsorption of NaCl in CF airways. 3. Clinical trials are under way using purinergic compounds such as the P2Y2 receptor agonist INS365. Activation of P2Y2 receptors has been found to both activate Cl, secretion and inhibit Na+ absorption. 4. The ultimate goal is to recover Cl, channel activity of mutant CFTR by either enhancing synthesis and expression of the protein or by activating silent CFTR Cl, channels. Strategies combining these drugs with compounds facilitating Cl, secretion and inhibiting Na+ absorption in vivo may have the best chance to counteract the ion transport defect in cystic fibrosis. [source] | ||||||||||