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Cystic fibrosis [keywords]
- Characterization of a Novel Two-Component System in Burkholderia cenocepacia. [JOURNAL ARTICLE]
- Curr Microbiol 2014 Dec 18.
Two-component systems are important regulatory systems that allow bacteria to adjust to environmental conditions, and in some bacteria are used in pathogenesis. We identified a novel two-component system in Burkholderia cenocepacia, an opportunistic pathogen that causes pneumonia in cystic fibrosis (CF) patients. The putative operon encodes BceS, a sensor kinase, and BceR, a response regulator. Our studies indicated that the bceR mutant showed a statistically significant decrease in protease, swimming motility, and quorum sensing when compared to the wild-type, but there was no significant difference in phospholipase C activity, swarming, and biofilm formation. In addition, the mutant showed a statistically significant reduction in virulence compared to the wild-type using the alfalfa plant model. Examination of the Burkholderia cepacia complex (a group of organisms that are phenotypically similar, but genotypically distinct) revealed that this system is prevalent in B. ambifaria, B. multivorans, B. vietnamiensis and B. dolosa. Interestingly, all these organisms have been associated with CF patients. The collective results indicate that BceSR influences various activities important in Burkholderia physiology and possibly pathogenesis. This information could be important in the design of novel therapeutics for Burkholderia infections.
- The effects of oscillating positive expiratory pressure therapy in adults with stable non-cystic fibrosis bronchiectasis: A systematic review. [JOURNAL ARTICLE]
- Chron Respir Dis 2014 Dec 17.
Airway clearance techniques (ACTs) are recommended for patients with stable non-cystic fibrosis (non-CF) bronchiectasis, but the efficacy of oscillating positive expiratory pressure (PEP) therapy compared to other techniques has not been reviewed. A systematic review of studies was conducted in stable patients comparing the effect of oscillating PEP therapy to other ACTs or a control condition. Data were extracted related to sputum expectoration, lung function, gas exchange, quality of life (QOL), symptoms, and exacerbation rate. Seven studies were included with a total of 146 patients, with a mean (SD) PEDro score of 7(1). Oscillating PEP therapy enhanced sputum expectoration compared to no treatment, but has equivalent benefits as the active cycle of breathing technique with gravity-assisted drainage (mean difference [95% CI] -2.8 g [-8.8 to 3.2 g]). Oscillating PEP has a similar effect as other ACTs on dynamic lung volumes, gas exchange and breathlessness. Use of oscillating PEP improved disease-specific QOL (p < 0.001) and cough-related QOL (p < 0.002) compared to no treatment but did not reduce exacerbation rate. In conclusion, in stable non-CF bronchiectasis, oscillating PEP therapy is associated with improvement in sputum expectoration and QOL compared to no treatment. Compared to other ACTs, the effect upon sputum expectoration, lung function, gas exchange, and symptoms are equivalent.
- Exposure to extremely low-frequency magnetic field affects biofilm formation by cystic fibrosis pathogens. [Journal Article]
- Future Microbiol 2014 Oct.:1303-17.
SUMMARY Aims: To evaluate the in vitro effects of extremely low-frequency magnetic field (ELF-MF) on growth and biofilm formation by Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia and Stenotrophomonas maltophilia strains from cystic fibrosis patients.The motion of selected ions (Fe, Ca, Cu, Zn, Mg, K, Na) was stimulated by the ion resonance effect, then influence on growth and biofilm formation/viability was assessed by spectrophotometry or viability count.Generally, exposure to ELF-MF significantly increased bacterial growth and affected both biofilm formation and viability, although with differences with regard to ions and species considered.Exposure to ELF-MF represents a possible new approach for treatment of biofilm-associated cystic fibrosis lung infections.
- Genetic and phenotypic heterogeneity in tropical calcific pancreatitis. [REVIEW]
- World J Gastroenterol 2014 Dec 14; 20(46):17314-17323.
Tropical calcific pancreatitis (TCP) is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world. The clinical phenotype of TCP has undergone marked changes since its first description in 1968. The disease is now seen in relatively older people with less severe symptoms. In addition, there are varying reports on the proportion of cases presenting with imaging abnormalities like calcification, ductal dilation, and glandular atrophy. Significant progress has also been made in understanding the etiopathology of TCP. The role of malnutrition and cassava toxicity in its pathogenesis is disproven and few studies have focused on the role of micronutrient deficiency and oxidative stress in the etiopathogenesis of TCP. Emerging evidence support an important role for genetic risk factors in TCP. Several studies have shown that, rather than mutations in trypsinogens, variants in serine protease inhibitor kazal type 1, cathepsin B, chymotrypsin C, cystic fibrosis transmembrane regulator, and carboxypeptidase A1, predict risk of TCP. These studies also provided evidence of mutational heterogeneity between TCP and chronic pancreatitis in Western populations. The current review summarizes recent advances that have implications in the understanding of the pathophysiology and thus, heterogeneity in genotype-phenotype correlations in TCP.
- Cystic fibrosis (CF) care through the patients' eyes - A nationwide survey on experience and satisfaction with services using a disease-specific questionnaire. [JOURNAL ARTICLE]
- Respir Med 2014 Dec 6.
The patients' perspective is an important aspect of quality management. A newly developed disease-specific questionnaire was used to assess the patients' experiences with care provided in specialised cystic fibrosis (CF) care centres.90 CF centres in Germany were invited to participate. Centre staff collected patient consent forms and sent the patients' addresses to the study centre. The questionnaires for adults and parents had 100 and 104 items respectively, with 3-6 response categories each. Items were dichotomised into "problem scores" (PS), indicating the presence or absence (PS 0%) of a reported problem.56 CF centres took part in the survey and recruited 1642 adults with CF and 1205 parents. The response rates were 74% in each group, with 1221 completed questionnaires from adults and 891 from parents. Participants reported good experiences with care. Factor analysis revealed 10 factors covering 70 items. Participants reported the best results for the factors "Physiotherapists" (PS 6%) and "Physician-Patient Relationship" (PS 9%). Factors with the highest problem scores were inpatient and outpatient "Facilities, Hygiene and Services". CF centres received reports of their own results and mean problem scores of all participating institutions. The problem scores differed considerably between CF centres.The nation-wide CF-specific patient experience survey identified specific shortcomings which were mainly related to communication, centre organisation, and facilities. Centre staff can use the results to improve the quality of care. We suggest that patients' views should become an integral component of efforts to promote patient-centred care.
- Symptoms of depression impact the course of lung function in adolescents and adults with cystic fibrosis. [JOURNAL ARTICLE]
- BMC Pulm Med 2014 Dec 16; 14(1):205.
Epidemiological studies report high rates of depression among patients with cystic fibrosis (CF). Assuming a causal relationship between depression and the progression of CF, our hypothesis is that elevated symptoms of depression would be a predictor of worse lung function after two years.In the context of the TIDES study, 473 German patients with CF (age 12-53 years, FEV1% predicted M = 66.2, range 13-137) completed the Hospital Anxiety and Depression Scale (HADS). Lung function (FEV1% predicted) was assessed at baseline and followed up two years later. Repeated measures analysis was performed involving the level of FEV1% and the level of depressive symptoms at baseline as independent factors and FEV1% at the 2-year follow-up as the dependent variable.Interaction between lung function and depression at baseline significantly affected the change in lung function at the 2-years observation interval. The largest decline in FEV1% occurred in depressed patients with good lung function at baseline. In contrast, patients without any clinically relevant depressive symptoms and with poor lung function at baseline showed a slight increase two years later.The findings emphasise the need to screen patients with CF for symptoms of depression and to treat co-morbid depression.
- A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation. [JOURNAL ARTICLE]
- ISME J 2014 Dec 16.
There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.The ISME Journal advance online publication, 16 December 2014; doi:10.1038/ismej.2014.234.
- Cigarette smoke and calcium conspire to impair CFTR function in airway epithelia. [Journal Article]
- Channels (Austin) 2014; 8(3):172-3.
To maintain health and function in response to inhaled environmental irritants and toxins, the lungs and airways depend upon an innate defense system that involves the secretion of mucus (i.e., mucin, salts, and water) by airway epithelium onto the apical surface to trap foreign particles. Airway mucus is then transported in an oral direction via ciliary beating and coughing, which helps to keep the airways clear. CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-regulated Cl(-) channel in the apical membrane of epithelium that contributes to salt and water secretion onto the luminal surface of airways, thereby ensuring that secreted mucus is sufficiently hydrated for movement along the epithelial surface. Dehydration of airway mucus, as occurs in cystic fibrosis, results in a more viscous, less mobile secretion that compromises the lung’s innate defense system by facilitating a build-up of foreign particles and bacterial growth. Related to this situation is chronic obstructive pulmonary disease (COPD), which is a leading cause of death globally. A major cause of COPD is cigarette smoking, which has been reported to decrease the cellular levels of CFTR in airway epithelia. In their recent article, Rasmussen and coworkers now report that exposure to cigarette smoke elevates cytosolic free Ca(2+) in airway epithelium, leading to decreased surface localization and cellular expression of CFTR and reduced levels of secreted airway surface liquid. Blocking this increase in cytosolic Ca(2+) largely prevented CFTR loss in airway epithelium and surprisingly, cellular lysosomes appear to be a major source for smoke-induced Ca(2+) elevation.
- Diabetes increases pancreatic fibrosis during chronic inflammation. [Journal Article, Research Support, Non-U.S. Gov't]
- Exp Biol Med (Maywood) 2014 Jun; 239(6):670-6.
Diabetes and fibrosis can be concurrent processes in several diseases such as cystic fibrosis or chronic pancreatitis. To evaluate whether diabetes can influence fibrosis and thus aggravate the pathological process, the progression of chronic pancreatitis was assessed in diabetic and non diabetic mice. For this purpose, insulin producing beta-cells in C57Bl/6J mice were selectively impaired by administration of streptozotocin. Chronic pancreatitis was then induced by repetitive administration of cerulein in normoglycaemic and hyperglycaemic mice. Diabetes caused enhanced collagen I deposition within three weeks of the onset of chronic pancreatitis and increased the proliferation of interstitial cells. This was accompanied by an increased number of interlobular fibroblasts, which expressed S100A4 (fibroblast-specific protein-1) and stimulation of α-smooth muscle actin expression of pancreatic stellate cells. In addition, the observed aggravation of chronic pancreatitis by diabetes also led to a significantly enhanced atrophy of the pancreas, increased infiltration of inflammatory chloracetate esterase positive cells and enhanced acinar cell death. We conclude that diabetes has a detrimental influence on the progression of chronic pancreatitis by aggravating fibrosis, inflammation and pancreatic atrophy.