How can we prevent multisystem complications of cystic fibrosis?

Cystic fibrosis (CF) is a multisystem disease. Some of this is accounted for by CF transmembrane regulator (CFTR) dysfunction in individual organs but in some cases this is compounded by the effects of systemic inflammation. The inflammation is in response to the chronic infection in the airways and is particularly important as a contributor to CF-related bone disease, CF-related diabetes mellitus, CF-related arthropathy, and vasculitis.

Bronchial epithelial cell growth regulation in fibroblast cocultures: the role of hepatocyte growth factor.

Proliferation of bronchial epithelial cells is an important biological process in physiological conditions and various lung diseases. The objective of this study was to determine how bronchial fibroblasts influence bronchial epithelial cell proliferation. The proliferative activity in cocultures was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct cells counts.

Clinical trials in cystic fibrosis.

In patients with cystic fibrosis (CF), clinical trials are of paramount importance. Here, the current status of drug development in CF is discussed and future directions highlighted. Methods for pre-clinical testing of drugs with potential activity in CF patients including relevant animal models are described.

Frequency of cytokine gene promoter polymorphisms in the Northern Ireland cystic fibrosis population.

It has been postulated that cytokine allele frequencies are gender and perhaps geographically-specific. Cytokine release is crucial in the regulation of the type and magnitude of the immune response. This study observed no differences in the frequency of cytokine promoter polymorphisms associated with variant levels of expression in patients with CF and a non-CF population of Northern Ireland.

The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis.

Decreased survival in patients with cystic fibrosis has been related to FEV1, BMI, and infection with Burkholderia cepacia complex (BCC). We have assessed the relationship of blood, sputum, and urine inflammatory markers to lung function, BMI, colonization with B cenocepacia (Bc), and patient survival. Thirty-nine stable cystic fibrosis (CF) patients (10 with Bc) were enrolled in a study to determine the effect of alpha-1-antitrypsin on airways inflammation.

The use of Raman microscopy to determine and localize vitamin E in biological samples.

Alpha-tocopherol (aT), the predominant form of vitamin E in mammals, is thought to prevent oxidation of polyunsaturated fatty acids. In the lung, aT is perceived to be accumulated in alveolar type II cells and secreted together with surfactant into the epithelial lining fluid. Conventionally, determination of aT and related compounds requires extraction with organic solvents.

Delivery of photosensitisers and light through mucus: investigations into the potential use of photodynamic therapy for treatment of Pseudomonas aeruginosa cystic fibrosis pulmonary infection.

Respiratory disease is the main cause of morbidity and mortality in patients with cystic fibrosis (CF). In such patients chronic Pseudomonas aeruginosa infection is virtually impossible to eradicate using antibiotic therapy. Photodynamic antimicrobial chemotherapy (PACT) could be one potential alternative antimicrobial method.

Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells.

Background: Staphylococcus aureus produces a set of proteins which act both as superantigens and toxins. Although their mode of action as superantigens is well understood, little is known about their effects on airway epithelial cells.

Methods: To investigate this problem, primary nasal epithelial cells derived from normal and asthmatic subjects were stimulated with staphylococcal enterotoxin A and B (SEA and SEB) and secreted (supernatants) and cell-associated (cell lysates) IL-8, TNF-alpha, RANTES and eotaxin were determined by specific ELISAs.

Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis.

Rationale: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.

Objectives: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.

Evidence for physical therapies (airway clearance and physical training) in cystic fibrosis: an overview of five Cochrane systematic reviews.

Background: A range of physical therapies (including airway clearance and physical training) are used in cystic fibrosis (CF). The aim of this paper is to summarise the main findings from Cochrane systematic reviews that have considered the evidence for physical therapies in CF.

Methods: All outcomes reported in relevant Cochrane systematic reviews are summarised.

Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis.

Neutrophil elastase (NE) is thought to be the most important protease which damages the cystic fibrosis (CF) lung. Attempts have been made to suppress this activity using the plasma-derived inhibitor, alpha(1)-antitrypsin (AAT). In this pilot study, the safety and efficacy of inhaled recombinant human AAT (rAAT) as a treatment for CF were investigated.

Cystic fibrosis sputum stimulates CD18-independent neutrophil migration across endothelial cells.

Excessive neutrophil recruitment to the lung underlies inflammatory-mediated lung damage in cystic fibrosis (CF). Neutrophils can migrate to the lung using either a CD18-dependent or CD18-independent mechanism. To determine if one of these migratory pathways is preferentially utilized by neutrophils migrating to the CF airways, this study examined the CD18 dependency of neutrophil transendothelial migration stimulated by the soluble fraction of CF sputum (SOL).

Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques versus Acapella.

Background: The efficacy of a new airway clearance device (Acapella) has not been previously investigated. Active cycle of breathing techniques (ACBT) is the standard airway clearance technique used in patients with bronchiectasis.

Objective: The objective of this study was to compare the efficacy of ACBT with Acapella as methods of airway clearance in adults with stable, productive bronchiectasis.

Effect of cystic fibrosis exacerbations on neutrophil function.

In cystic fibrosis (CF), inflammation is caused by persistent bacterial infection from Pseudomonas aeruginosa and Burkholderia cenocepacia in the lung and is characterised by the persistent infiltration of massive numbers of neutrophils which leads to lung injury. The aim of this present study was to investigate the effects of CF exacerbations on the reactivity of peripheral blood neutrophils compared to data from a normal healthy control population. Peripheral blood neutrophils were isolated from control subjects and CF patients before and after an exacerbation of their lung disease.

Hypersensitivity pneumonitis associated with mushroom worker's lung: an update on the clinical significance of the importation of exotic mushroom varieties.

Hypersensitivity pneumonitis remains an important industrial disease in mushroom workers. It has a significant morbidity, and early diagnosis and removal from exposure to the antigen are critically important in its management. Recently, several new allergens have been described, particularly those from mushroom species originating in the Far East, which are of clinical significance to workers occupationally exposed to such allergens in cultivation, picking, and packing of commercial mushroom crops.

Early detection of Pseudomonas aeruginosa--comparison of conventional versus molecular (PCR) detection directly from adult patients with cystic fibrosis (CF).

Background: Pseudomonas aeruginosa (PA) is the most important bacterial pathogen in patients with cystic fibrosis (CF) patients. Currently, routine bacteriological culture on selective/non- selective culture media is the cornerstone of microbiological detection. The aim of this study was to compare isolation rates of PA by conventional culture and molecular (PCR) detection directly from sputum.

Epidemiology of Burkholderia cepacia complex species recovered from cystic fibrosis patients: issues related to patient segregation.

Studies of the prevalence of Burkholderia cepacia complex species amongst cystic fibrosis (CF) patients in different geographical regions, and the association between cross-infection and putative transmissibility markers, will further our understanding of these organisms and help to address infection-control issues. In this study, B. cepacia complex isolates from CF patients in different regions of Europe were analysed.

Infection control and the significance of sputum and other respiratory secretions from adult patients with cystic fibrosis.

Background: There is limited data available on the environmental and public health impact of the microbiological hazards associated with sputa from patients with cystic fibrosis [CF]. Pseudomonas aeruginosa, Burkholderia cenocepacia (formerly Burkholderia cepacia genomovar III), Staphylococcus aureus and Stenotrophomonas maltophilia are bacterial pathogens which are commonly found in the sputum of CF patients. A study was performed to ascertain the amount of sputum produced relating to microbial loading, as well as the diversity of bacteria present in a population of adult patients, with particular attention to pathogenic organisms.

Bronchiectasis in secondary care: a comprehensive profile of a neglected disease.

Background: Bronchiectasis is poorly characterised in secondary care. Methods: Over 6 months, 410 bronchiectasis patients attended our clinics. One hundred randomly selected patients were characterised in detail.

Development of a diagnostic PCR assay that targets a heat-shock protein gene (groES) for detection of Pseudomonas spp. in cystic fibrosis patients.

Laboratory detection of Pseudomonas spp., in particular Pseudomonas aeruginosa, remains an important assay in the management of patients with cystic fibrosis (CF). As the groES and groEL genes of P.