Objective: Sleep, well-being and quality of life (QOL) are important considerations in Cystic Fibrosis (CF) management.Furthermore, physical activity (PA) should be monitored and encouraged as it can improve patient health.The objective of this study was to establish a biopsychological profile of adults with CF and assess PA and sedentary behaviour levels.Methods: Observational study which assessed QOL, wellbeing, sleep and PA levels in adults with CF, at University Hospital Limerick.Participants were included if they were medically stable, with no exacerbation in the previous month.Wellbeing was assessed by the Alfred Wellness Score (AWE), sleep quality by the Pittburgh Sleep Quality Index (PSQI) and QOL using the CF Questionnaire-Revised (CFQ-R).PA and sedentary behaviour were assessed using an ActivPAL accelerometer which was worn for seven days.Sedentary behaviour consisted of both lying and sitting postures, as the ActivPAL cannot distinguish between these positions.Results: Thirty-three participants (13M/20F; 26.2 ± 7.1 years) were recruited.Mean FEV1 was 72.9% (±26.2SD).CFQ-R (respiratory domain) was 76.3% (±14.9SD) and mean AWE score was 69.5 (± 12.6 SD) indicating very good levels of wellbeing and QOL.Mean step count was 7788 (± 3583 SD).Over 75% of participants did not reach recommended PA targets (>10,000 steps), with females being 25% less active than males.Mean sedentary time was 18.6 (±2.1 SD) hours per day.The mean PSQI score was 5.7 (± 3.9 SD).Sixteen (48.5%) participants scored >5, indicating poor sleep quality.Pearson correlation co-efficients indicated that poor sleep quality was significantly negatively correlated with low step counts (-0.713, p = 0.000) and positively correlated with higher sedentary time (0.681, p = 0.000). Conclusion:The majority of participants did not meet PA guidelines.PA and sedentary behaviour levels correlate to self-reported sleep quality and this should be considered in PA interventions.

Objectives: Microbial lung infection plays a major role in morbidity and mortality in cystic fibrosis (CF) and bronchiectasis patients. Multiple bacterial species are often present in one sputum sample. The aim of this study is to compare the microbiota of sputum present in CF chronic lung infection and bronchiectasis patients. Methodology: In this study, sputum samples from adult CF (n=18) and bronchiectasis (n=15) patients were subject to terminal restriction fragment length polymorphism (TRFLP) and bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) analysis to identify and compare different bacterial species and abundance present. Results: TRFLP and bTEFAP gave consistent microbiome results for each sputum sample. Both TRFLP and bTEFAP showed that Pseudomonas aeruginosa and Burkholderia cepacia were the most prevalent in both CF and bronchiectasis lung. The overall microbiomes are similar between CF and bronchiectasis patient lungs with lower microbiome diversity in CF patients. Conclusion: This comparison shows some strong similarity between microbiomes of chronic CF lung infection and bronchiectasis, which may explain why many interventions that are demonstrated to be effective in CF have also been found to be effective in bronchiectasis.

Background: CF is a genetically inherited disease that causes pulmonary secretion retention, leading to chronic infection and progressive lung damage. This progressive disease course is interspersed with acute exacerbations, which are often treated with admission to hospital for intravenous antibiotics and intensive physiotherapy to promote clearance of secretions from the airways.

Background: This study examined characteristics of adult and adolescent patients with cystic fibrosis (CF) to determine factors associated with an increased risk of pulmonary exacerbations. Methods: 249 patients with CF infected with multidrug resistant bacteria were recruited and prospectively followed for up to 4.5 years until they experienced a pulmonary exacerbation severe enough to require intravenous antibiotics. Multivariable regression analyses were used to compare the characteristics of patients who experienced an exacerbation with those who did not. Results: 124 of the 249 patients (50%) developed a pulmonary exacerbation during the first year and 154 (62%) experienced an exacerbation during the 4.5 year study period. Factors predictive of exacerbations in a multivariable survival model were younger age (OR 0.98, 95% CI 0.96 to 0.99), female sex (OR 1.45, 95% CI 1.07 to 1.95), lower forced expiratory volume in 1 second (FEV1) (OR 0.98, 95% CI 0.97 to 0.99), and a previous history of multiple pulmonary exacerbations (OR 3.16, 95% CI 1.93 to 5.17). Chronic use of inhaled corticosteroids was associated with an increased risk of exacerbation (OR 1.92, 95% CI 1.00 to 3.71) during the first study year. Conclusions: Patients who experience pulmonary exacerbations are more likely to be younger, female, using inhaled steroids, have a lower FEV1, and a history of multiple previous exacerbations. It is hoped that knowledge of these risk factors will allow better identification and closer monitoring of patients who are at high risk of exacerbations.

Background We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.Methods 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870.Findings 132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% Cl 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups.Interpretation Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 microg ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.

Reported actuarial one-year survival for patients with cystic fibrosis (CF) after lung transplant is 55-91%. Infection is the most common cause of early death. Colonization with Burkholderia cepacia complex is associated with reduced survival and international lung transplant referral guidelines support individual unit assessment policies for patients colonized with other pan-resistant bacteria. We examined local data on survival after transplant for CF to determine the impact of colonization with pan-resistant bacteria. A retrospective review of all CF patients from Royal Prince Alfred Hospital (RPAH), Sydney, who underwent lung transplantation at St Vincent's Hospital, Sydney, 1989-2002, was performed. Sixty-five patients were listed for lung transplantation with 54 (male: female=29:25) receiving transplants. Of the 11 patients (17%) who died on the waiting list, six were colonized with pan-resistant Pseudomonas aeruginosa. Thirty of the 54 transplanted patients had at least one pan-resistant organism before transplant. In 28 this included P. aeruginosa. Overall one-year survival was 92% with a median survival of 67 months. Overall survival for the pan-resistant group (N = 30) was not significantly different to survival in those with sensitive organisms (N = 24) (Logrank chi square = 1.6, P = 0.2). Three patients colonized with B. cepacia complex pre-transplant survive at 11, 40 and 60 months post-transplant. Infection contributed to 11 of the 18 post-transplant deaths, with pre-transplant-acquired bacterial pathogens responsible in two cases. Patients continued to acquire multiresistant bacteria post-transplantation. Lung transplant survival at St Vincent's Hospital for CF adults from RPAH compares favourably with international benchmarks. Importantly, colonization with pan-resistant bacteria pre-transplant did not appear to adversely affect survival post-transplant.

Recent advances in molecular typing techniques have led to the identification of a dominant clonal strain of Pseudomonas aeruginosa within several cystic fibrosis (CF) clinics ([2][1]-[6][2], [8][3], [9][4]). These strains have been described as “hypertransmissible,” and “patient-to-patient

ABSTRACT Genetic investigations were carried out with 50 phenotypically selected strains of Pseudomonas aeruginosa from 18 patients attending an Australian cystic fibrosis (CF) center. The isolates were analyzed by restriction fragment length polymorphism (RFLP) analysis by pulsed-field gel electrophoresis (PFGE). Phylogenetic analysis of the macrorestriction patterns showed rates of genetic similarity ranging from 76 to 100%; 24 (48%) of the strains from 11 patients had greater than 90% similarity. A dominant strain emerged: 15 isolates from seven patients had identical PFGE patterns, and 4 other isolates were very closely related. The 50 isolates were grouped into 21 pulsotypes on the basis of visual delineation of a three-band difference. Ten of the 18 (56%) patients were infected with clonal or subclonal strains. Sequence analysis of PCR products derived from the mucA gene showed 20 mutations, with the number of mutations in individual isolates ranging from 1 to 4; 19 of these changes are reported here for the first time. Potentially functional changes were found in 22 (44%) isolates. Eight changes (five transversions and three single base deletions) led to premature stop codons, providing support for the presence of mucA mutations as one pathway to mucoidy. There was a trend toward an association between the dominant strain and lack of potentially functional mucA mutations ( P = 0.09 by the χ 2 test) but no relationship between genotype and phenotype. This is the first study of genetic variation in P. aeruginosa isolates from adult Australian CF patients. The findings highlight the need for further investigations on the transmissibility of P. aeruginosa in CF patients.