Optimising the care and quality of life of people with cystic fibrosis: the influence of cystic fibrosis transmembrane conductance regulator modulators.

Cystic fibrosis is a life-limiting, inherited, multi-organ disease which affects many systems of the body. Until recently, treatments were only able to ameliorate symptoms, but the introduction of precision medications which modulate the underlying defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene has changed this. Notably improvements in nutrition and lung function, reduced use of antibiotics and reduced occupation rates for hospital beds have been seen. This article summarises the discussion of a group of healthcare professionals from different specialties and an expert patient, representing their personal views and experience of treating patients who are using CFTR modulators. The discussion was sponsored by an unrestricted grant from Chiesi Limited (Manchester, UK).

Branch retinal vein occlusion in an asymptomatic adult with cystic fibrosis.

PURPOSE: This article aims to describe a case of asymptomatic branch retinal vein occlusion (BRVO) in a patient with cystic fibrosis (CF) and discuss the possible link between the two. CASE REPORT: A young adult (aged 35 years) with CF who presented for routine ocular examination was found to have a superior temporal BRVO in the left eye. Visual acuity was unaffected, measuring -0.06 LogMAR, and intraocular pressure was 10 mm Hg. Optical coherence tomography showed no macular involvement. Regarding the patient's general health, blood pressure was within the normal range, and there was no diabetes. Exploratory blood tests revealed elevated fibrinogen levels. CONCLUSIONS: It is hypothesized that BRVO occurred secondary to raised fibrinogen levels, a common feature in CF resulting from chronic pulmonary infection and inflammation. Practitioners should be aware of the possible link between BRVO and CF.

The development and validation of the major life changing decision profile (MLCDP).

BACKGROUND: Chronic diseases may influence patients taking major life changing decisions (MLCDs) concerning for example education, career, relationships, having children and retirement. A validated measure is needed to evaluate the impact of chronic diseases on MLCDs, improving assessment of their life-long burden. The aims of this study were to develop a validated questionnaire, the "Major Life Changing Decision Profile" (MLCDP) and to evaluate its psychometric properties. METHODS: 50 interviews with dermatology patients and 258 questionnaires, completed by cardiology, rheumatology, nephrology, diabetes and respiratory disorder patients, were analysed for qualitative data using Nvivo8 software. Content validation was carried out by a panel of experts. The first version of the MLCDP was completed by 210 patients and an iterative process of multiple Exploratory Factor Analyses and item prevalence was used to guide item reduction. Face validity and practicability was assessed by patients. RESULTS: 48 MLCDs were selected from analysis of the transcripts and questionnaires for the first version of the MLCDP, and reduced to 45 by combination of similar themes. There was a high intraclass correlation coefficient (0.7) between the 13 members of the content validation panel. Four more items were deleted leaving a 41-item MLCDP that was completed by 210 patients. The most frequently recorded MLCDs were decisions to change eating habits (71.4%), to change smoking/drinking alcohol habits (58.5%) and not to travel or go for holidays abroad (50.9%).Factor analysis suggested item number reduction from 41 to 34, to 29, then 23 items. However after taking into account item prevalence data as well as factor analysis results, 32 items were retained. The 32-item MLCDP has five domains education (3 items), job/career (9), family/relationships (5), social (10) and physical (5). The MLCDP score is expressed as the absolute number of decisions that have been affected. CONCLUSIONS: The 32-item (5 domains) MLCDP has been developed as an easy to complete generic tool for use in clinical practice and for quality of life and epidemiological research. Further validation is required.

Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum.

BACKGROUND: Bacteria from the Burkholderia cepacia complex (Bcc) are the only group of cystic fibrosis (CF) respiratory pathogens that may cause death by an invasive infection known as cepacia syndrome. Their large genome (> 7000 genes) and multiple pathways encoding the same putative functions make virulence factor identification difficult in these bacteria. METHODS: A novel microarray was designed to the genome of Burkholderia cenocepacia J2315 and transcriptomics used to identify genes that were differentially regulated when the pathogen was grown in a CF sputum-based infection model. Sputum samples from CF individuals infected with the same B. cenocepacia strain as genome isolate were used, hence, other than a dilution into a minimal growth medium (used as the control condition), no further treatment of the sputum was carried out. RESULTS: A total of 723 coding sequences were significantly altered, with 287 upregulated and 436 downregulated; the microarray-observed expression was validated by quantitative PCR on five selected genes. B. cenocepacia genes with putative functions in antimicrobial resistance, iron uptake, protection against reactive oxygen and nitrogen species, secretion and motility were among the most altered in sputum. Novel upregulated genes included: a transmembrane ferric reductase (BCAL0270) implicated in iron metabolism, a novel protease (BCAL0849) that may play a role in host tissue destruction, an organic hydroperoxide resistance gene (BCAM2753), an oxidoreductase (BCAL1107) and a nitrite/sulfite reductase (BCAM1676) that may play roles in resistance to the host defenses. The assumptions of growth under iron-depletion and oxidative stress formulated from the microarray data were tested and confirmed by independent growth of B. cenocepacia under each respective environmental condition. CONCLUSION: Overall, our first full transcriptomic analysis of B. cenocepacia demonstrated the pathogen alters expression of over 10% of the 7176 genes within its genome when it grows in CF sputum. Novel genetic pathways involved in responses to antimicrobial resistance, oxidative stress, and iron metabolism were revealed by the microarray analysis. Virulence factors such as the cable pilus and Cenocepacia Pathogenicity Island were unaltered in expression. However, B. cenocepacia sustained or increased expression of motility-associated genes in sputum, maintaining a potentially invasive phenotype associated with cepacia syndrome.