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ABSTRACT: BACKGROUND: Pseudomonas aeruginosa and Aspergillus fumigatus frequently co-colonise the airways of patients with cystic fibrosis (CF). This study aimed to assess the impact of short-term administration of intravenous antipseudomonal antibiotics during CF exacerbations on the presence of Aspergillus. METHODS: Pre- and post-antibiotic sputum samples from 26 adult patients with CF and chronic Pseudomonas colonisation were analysed for the presence of Aspergillus by fungal culture, real-time PCR and galactomannan antigen (GM). Lung function (forced expiratory volume in 1 s and forced vital capacity % predicted) and blood levels of total IgE, specific A fumigatus IgE and specific A fumigatus IgG were measured at the start and end of antibiotics. Respiratory viral real-time PCR and bacterial community profiling using ribosomal intergenic spacer analysis (RISA) were performed to estimate concurrent changes in the lung microbiome. RESULTS: Aspergillus PCR and GM were more sensitive than culture in detecting Aspergillus species (culture 8%, GM 31%, PCR 77%). There was a significant decline in the presence of Aspergillus, measured both by PCR and GM index, following antibacterial therapy (PCR: median increase in crossing threshold 1.7 (IQR 0.5-3.8), p<0.001; GM: median fall in GM index 0.7 (IQR 0.4-1.6), p=0.016). All patients improved clinically with a significant increase in lung function (p<0.0001). RISA community analysis showed large changes in bacterial community similarity in 67% of patients following antibiotics. Viral RT-PCR demonstrated the presence of a concurrent respiratory virus in 27% of patients. CONCLUSIONS: Intravenous antibiotics targeting Pseudomonas during CF pulmonary exacerbations have a negative impact on the presence of Aspergillus in sputum samples.
Thorax 03/2013; · 6.84 Impact Factor
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ABSTRACT: BACKGROUND: Although there have been case reports of hypothalamic-pituitary-adrenal (HPA) axis suppression in patients with cystic fibrosis (CF) caused by the combination of oral itraconazole and inhaled fluticasone, to date no study has assessed the incidence of this potentially serious side effect. METHODS: Synacthen tests were conducted on all patients with CF receiving itraconazole and inhaled fluticasone and an equal number of patients with CF receiving inhaled fluticasone but not itraconazole. Itraconazole levels were measured in patients receiving the therapy. RESULTS: Twelve patients receiving itraconazole and fluticasone underwent synacthen tests. All 12 had abnormal synacthen test results and 10/12 (83%) had HPA axis suppression. Two patients had severe HPA axis suppression with a peak cortisol <75nmol/L and further 3 patients had moderately severe suppression with a peak cortisol <250nmol/L. In contrast, only 2/12 on fluticasone alone had HPA axis suppression (both mild). The median (range) basal cortisol levels were significantly lower in those patients receiving itraconazole and inhaled fluticasone compared to those on fluticasone alone (219(22-508)nmol/L v 348(41-738)nnmol/L, p=0.02), similar results were seen for peak cortisol levels (404(59-706)nmol/L v 672(432-1178)nmol/L, p<0.001) and cortisol rise (179(37-240)nmol/L v 368(210-539)nmol/L, p<0.001). The median (range) itraconazole level was 5.5(1.7-14.7)mg/L. Neither itraconazole levels nor fluticasone dose correlated with the degree of adrenal suppression. CONCLUSIONS: In this study, all patients receiving itraconazole and inhaled fluticasone had abnormal synacthen test results. The incidence of HPA axis suppression with this treatment combination appears to be higher than that previously reported with itraconazole and inhaled budesonide.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 12/2012; · 3.19 Impact Factor
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ABSTRACT: The SPACE study will assess exhaled breath hydrogen cyanide (HCN) concentrations as a marker of Pseudomonas aeruginosa (PA) infection in 240 children with cystic fibrosis (CF). It will use off-line selected ion flow tube mass spectrometry (SIFT-MS) analysis and so we needed to investigate which breath sampling bag material to use, the maximum storage time before analysis and the benefit of warming the bag samples. We studied 15 children with CF, 8 had chronic PA infection and 7 did not. Each exhaled directly into the instrument (on-line) and also into two 25 µm thick Nalophan (25N), two 70 µm Nalophan (70N) and two Tedlar® bags. Bags were stored at 20 or 37 °C. HCN concentrations were analysed at 1, 6, 24 and 48 h (off-line). Acetone and water vapour concentrations were also measured in parallel. Correlation between on-line and off-line concentrations measured by SIFT-MS was better for all compounds and bag types at 37 °C. The median (IQR) on-line HCN concentration was 8.9(4.4-13.7) parts per billion by volume, ppbv. Both on-line and off-line HCN concentrations were significantly higher in patients with PA infection than those without. At 37 °C the correlation between on-line and off-line HCN concentrations was good up to 6 h in the 25N bag (R(2) = 0.79) and up to 24 h for the 70N and Tedlar bags (R(2) = 0.82 and 0.86). The correlation between on- and off-line acetone concentrations at 37 °C was good up to 24 h in 25N, 70N and Tedlar bags (R(2) = 0.89, 0.93 and 0.97). In all three types of bag the water vapour concentration fell quickly and by 24 h was equivalent to that of lab air. Samples stored in Tedlar or 70N bags, warmed to 37 °C and analysed within 24 h, give HCN and acetone concentrations which correlate well with on-line measurements.
Journal of Breath Research 07/2012; 6(3):036004. · 2.54 Impact Factor
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ABSTRACT: The authors present the case of an older patient with cystic fibrosis (CF) and recurrent haemoptysis complicated by acute pulmonary embolism. The patient was treated successfully with a combination of anticoagulation and bronchial artery embolisation. The management of CF-related haemoptysis, the impact of an ageing CF population and the incidence of thromboembolic disease in CF are discussed.
Thorax 06/2012; 67(10):931-2. · 6.84 Impact Factor
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Journal of the Royal Society of Medicine 06/2012; 105 Suppl 2:S44-9. · 1.41 Impact Factor
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ABSTRACT: BACKGROUND: We examined pulmonary artery pressure (PAP) characteristics of CF adults, studied clinical correlates and long-term survival. METHODS: Comprehensive clinical data were collected and Doppler echocardiography was used to estimate PAP in 109 stable CF adults and 50 healthy controls. RESULTS: CF patients had lower day and night-time oxygen status, elevated CRP and BNP, and elevated PAP (27.7(13.2, 62.8) mmHg patients v 17.9(11.3, 30.9) mmHg controls, p<0.001). Even patients with mild pulmonary disease had raised PAP. PAP measurements strongly correlated with arterial partial pressure of oxygen (PaO(2), r=-0.673, p<0.001), and FEV(1) percentage predicted (FEV(1)%, r=-0.642, p<0.001) which were both independent predictors of PAP. At 10year follow up PAP measurements were related to survival but FEV(1)% and PaO(2) were both stronger predictors of death. CONCLUSIONS: PAP is raised in CF adults and correlates with pulmonary disease severity. Unlike PaO(2) and FEV(1)%, it does not appear to be an independent prognostic marker.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 05/2012; · 3.19 Impact Factor
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ABSTRACT: Burkholderia cepacia complex (BCC) is a group of 17 closely related bacterial species that can cause pulmonary infection in patients with cystic fibrosis (CF). The clinical manifestations of BCC infection are varied but can include cepacia syndrome, which is a rapidly progressing necrotising pneumonia with an almost universally fatal outcome. We report the case of a 38year old man, known to have chronic infection with the ET12 strain of Burkholderia cenocepacia who developed cepacia syndrome 26years after initial infection. Aggressive treatment with a combination of 4 intravenous antibiotics, oral corticosteroids and cyclosporin brought about clinical, radiological and biochemical resolution of his cepacia syndrome. This case highlights the possible role of cyclosporin in the treatment of cepacia syndrome.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 04/2012; 11(5):458-60. · 3.19 Impact Factor
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ABSTRACT: Non-invasive ventilation (NIV) is accepted as a bridge to lung transplantation in cystic fibrosis (CF) but there is little evidence to support its use outside this setting.
We reviewed the records of all patients with CF who received domiciliary NIV at our centre between 1991 and 2010.
Of 47 patients studied, 36% underwent lung transplantation, 28% died without transplantation and 30% remain alive on NIV. Median duration of NIV was 16 months (range 2-90). Mean FEV(1) fell by 212 ml over the year before NIV but increased by 18 ml in the following year (p<0.01). Individual response to NIV was associated with lower baseline and more rapid decline in FEV(1). From 1991 to 2000, 70% underwent lung transplantation; from 2001 to 2010 only 27% were transplanted.
NIV may slow or reverse the decline in lung function in advanced CF. NIV is increasingly used beyond a bridge to transplantation at our centre.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 12/2011; 11(3):187-92. · 3.19 Impact Factor
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ABSTRACT: Despite their high bacterial load, bacteraemia is rare in patients with cystic fibrosis (CF). We report an adult with CF who developed Pseudomonas aeruginosa bacteraemia during an episode of acute appendicitis. The Pseudomonas aeruginosa isolated from the blood culture was confirmed by molecular typing to be the same transmissible strain responsible for the patient's chronic pulmonary infection. We hypothesise that this patient's bacteraemia was caused by Pseudomonas aerunginosa in swallowed sputum, crossing the inflamed appendiceal wall and entering the blood stream.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 07/2011; 10(6):477-8. · 3.19 Impact Factor
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ABSTRACT: Vasculitis is a well recognised complication of Cystic Fibrosis. Corticosteroids are the mainstay of treatment but some cases can be resistant and may require additional disease modifying agents. We describe a case of steroid resistant cutaneous vasculitis which was successfully treated with chloroquine in addition to corticosteroids and a subsequent relapse with chloroquine alone.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 12/2010; 9(6):439-41. · 3.19 Impact Factor
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Journal of the Royal Society of Medicine 07/2010; 103 Suppl 1:S15-9. · 1.41 Impact Factor
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ABSTRACT: Although there is now compelling evidence for cross-infection by strains of Pseudomonas aeruginosa at some specialist (cystic fibrosis [CF]) centers, the clinical impact of infection by transmissible strains is unclear.
In an 8-year prospective study, we compared the clinical outcome of two groups of patients with CF infected by transmissible (n = 28) and sporadic strains (n = 52) of P aeruginosa.
There were no differences between the two groups in survival, annual changes in spirometry, or BMI. There were differences in requirements for IV antibiotic treatment (mean [SD]: 29.3 [21.9] days vs 53.1 [32.5] days) and hospitalization (median [range]: 11.6 [1.1, 49.3] days vs 23.3 [5.5, 103.6] days) between patients infected with sporadic and transmissible strains of P aeruginosa, respectively.
We conclude that infection by transmissible P aeruginosa does not increase mortality but is associated with increased health-care and antibiotic use for patients with CF.
Chest 06/2010; 137(6):1405-9. · 5.25 Impact Factor
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ABSTRACT: Advances in the management of cystic fibrosis have led to a significant improvement in survival, although marked differences between individuals are still observed. The value of patient-reported health-related quality of life scores in predicting survival in adults with cystic fibrosis is unknown.
To evaluate whether patient-reported health-related quality of life could predict survival in cystic fibrosis.
From 1996 to 1997 a consecutive series of 223 patients were recruited to evaluate the Cystic Fibrosis Quality of Life Questionnaire. Demographic (age, sex), clinical (FEV(1)% predicted, body mass index, diabetes, B. Cepacia complex, intravenous access device, nutritional and lung transplant status) and health-related quality of life variables were recorded (Cystic Fibrosis Quality of Life Questionnaire and the SF-36). These data were used as baseline measures to explore the prognostic association of health-related quality of life and subsequent survival.
At the census date (December 31, 2006) 154 (69.1%) adults were alive, 66 (29.6%) had died, and three (1.3%) were lost to follow-up. Cox proportional hazards models and bootstrapping procedures examined if health-related quality of life domains predicted survival after adjusting for the demographic and clinical factors. The physical functioning domain of the Cystic Fibrosis Quality of Life Questionnaire and the pain domain of the Short Form-36 had the strongest statistical associations with survival.
Aspects of patient-reported quality of life serve as prognostic measures of survival beyond a number of previously known factors in cystic fibrosis. This needs to be investigated further in a larger longitudinal study.
American Journal of Respiratory and Critical Care Medicine 11/2008; 179(1):54-8. · 11.08 Impact Factor
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ABSTRACT: Achieving and maintaining an ideal nutritional status is the primary aim of the nutritional management of cystic fibrosis (CF). It is unclear how nutritional interventions impact on patients' perceptions and behaviours concerning body image and eating. This work aimed to provide a psychosocial profile and compare CF patients receiving (a) enteral tube feeding, (b) nutritional supplements, (c) no nutritional interventions, and (d) healthy controls.
A cross-sectional questionnaire design was employed. Age, gender, lung function, and body mass index were recorded. Subjects completed measures of eating attitudes, perceived and desired body shape, body image, self-esteem and quality of life (QoL).
A minority of CF patients reported disordered eating. Those receiving nutritional interventions engaged in less dieting behaviour. All CF groups, especially intervention groups, received more pressure from others to eat. For females, control groups desired to be slimmer whereas intervention groups desired to be heavier. Healthy males were content with their body whereas CF males wished to be heavier. Patients receiving enteral tube feeding were less satisfied with their body image, reported lower self-esteem and poorer QoL.
Body image and eating behaviours are important considerations of nutritional interventions for maintaining QoL.
Clinical Nutrition 02/2007; 26(1):91-9. · 3.73 Impact Factor
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Journal of Pediatrics 01/2007; 149(6):884-5; author reply 885. · 4.11 Impact Factor
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ABSTRACT: A number of transmissible Pseudomonas aeruginosa strains have been identified which potentially constitute an emerging threat to patients with cystic fibrosis (CF). We sought to identify DNA markers that were specific to a transmissible P. aeruginosa CF clone and evaluate these probes on a large collection of genotypically distinct P. aeruginosa strains. Using subtractive DNA hybridization, in combination with analysis using the P. aeruginosa PAO1 genome chip, DNA markers specific for or absent from the Manchester transmissible CF strain (MA) were identified. Five subtractive DNA hybridization markers (MA15, MA18, MA21, MA22, and MA30) were found to be specific to strain MA and were located within a novel 13,318-bp genomic island, designated the MA island. The MA island encoded 18 genes and consisted of two bacteriophage-like regions; one region encoded the MA-specific subtractive hybridization markers, while the other bacteriophage-like region contained a Vibrio cholera-like toxin gene. Probes MA15, MA18, MA21, MA22, and MA30 were all found to be specific to strain MA when a collection of 141 P. aeruginosa strains was examined by hybridization with each DNA marker. In contrast, a previously isolated DNA marker for the Liverpool transmissible CF strain, PS21, was not found to be specific, detecting two additional strain types in the collection screened. Both the Manchester and Liverpool strain types were not encountered in CF populations outside the United Kingdom. The MA genomic island and Vibrio cholera-like toxin gene within it constitute novel genetic factors associated with a transmissible P. aeruginosa strain and their role in pathogenesis remains to be determined.
American Journal of Respiratory Cell and Molecular Biology 08/2005; 33(1):56-64. · 5.13 Impact Factor
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ABSTRACT: The disease progression of cystic fibrosis (CF) is marked by an increase in clinical conditions and therapeutic interventions, which have the potential to affect health-related quality of life (HRQoL). This cross-sectional study explored associations between clinical variables and HRQoL.
HRQoL was measured using the Cystic Fibrosis Quality of Life (CFQoL) questionnaire, which consists of nine domains: physical, social, treatment, chest symptoms, emotional functioning, concerns for the future, relationships, body image, and career concerns. The CFQoL was completed by 223 adults with CF. Clinical and demographic data collected were: age, gender, FEV1% predicted, BMI, Burkholderia cepacia status, lung transplant status, diabetic status, level of nutritional intervention, and presence of an intravenous access device. Multiple regression using forward selection was used to construct models relating these variables to each HRQoL domain.
Despite many of the variables being inter-related, some variables were associated with CFQoL domains even in the presence of other important clinical factors. FEV1% predicted was weakly positively associated with all nine domains. Strong evidence emerged that patients who had received a lung transplant reported a higher HRQoL in physical and social functioning, chest symptoms, and treatment issues. Females tended to report a lower quality of life for chest symptoms and career issues, but higher values for body image. Patients with an access device expressed more career concerns. There was no evidence of an association between B. cepacia and any of the nine CFQoL domains. The model for the body image domain explained a high percentage of the variance (R2=30%): negative body image was associated with lower BMI, having an access device, diabetes, and enteral feeding.
While important associations were identified, much of the variance in HRQoL remains unexplained. Other clinical and psychosocial variables merit investigation. A longitudinal study is required to investigate how the disease trajectory and associated treatments affect an individual's quality of life.
Journal of Cystic Fibrosis 04/2005; 4(1):59-66. · 3.19 Impact Factor
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ABSTRACT: We have performed a 4-year prospective surveillance for Pseudomonas aeruginosa cross-infection at a large regional adult cystic fibrosis center. Despite purpose-built facilities in a new building and the practice of strict hygiene, P. aeruginosa cross-infection has continued. In contrast, individuals segregated from the cohort of patients with chronic P. aeruginosa infection but who attend the same center have not acquired infection with transmissible P. aeruginosa strains. Simple infection control measures alone do not prevent the spread of transmissible P. aeruginosa strains between individuals with cystic fibrosis. However, in our clinic patient segregation effectively controlled spread of such strains.
American Journal of Respiratory and Critical Care Medicine 03/2005; 171(3):257-60. · 11.08 Impact Factor
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ABSTRACT: This study aimed to produce valid patient-based UK National Health Service (NHS) costs for adults with cystic fibrosis to identify differences between hospital- and home-based treatments for infections.
A costing study was carried out in adults with cystic fibrosis (CF) in the United Kingdom, who required intravenous antibiotic treatments for respiratory infections, administered either at home or in the hospital. The perspective was that of the NHS hospital trust. Data were collected retrospectively for each patient for 1 year using clinical records. Data were collected for 116 adults with CF between 2000 and 2001, when 42,382 treatment days (454 courses) of intravenous antibiotics were administered; 213 courses with intention-to-treat at home and 241 courses with intention-to-treat in the hospital. The mean length of a course was 15.3 days.
Patients who had >60 percent of courses at home over 1 year had a mean cost of 13,528 UK pounds, compared with 22,609 pounds for patients who had > 60 percent of courses in the hospital, and a mean cost of 19,927 UK pounds for patients who had an equal mix of home and hospital care (p = .0001).
The key cost-generating events in CF respiratory infections are hospital admissions. Future studies assessing costs should concentrate on factors affecting admissions, length of stay, staff input, and alternative methods of home-care provision, rather than marginal effects, such as using different antibiotics.
International Journal of Technology Assessment in Health Care 02/2005; 21(4):506-10. · 1.37 Impact Factor
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ABSTRACT: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis and might be related to calcium and vitamin D malabsorption from the gastrointestinal tract. The aim of this study was to investigate the effect of calcium and vitamin D supplementation on BMD and bone metabolism in these subjects.
Patients were invited to participate if they had a BMD Z score of -1 or less in the lumbar spine, proximal femur or distal forearm. Patients were randomised to receive calcium 1 g+vitamin D 800 IU or placebo daily, in addition to their regular vitamin D supplements (900 IU/day). BMD and bone biochemical markers were measured before and after 1 year of treatment.
After 12 months, the treatment group (n=15) showed a reduced rate of bone loss compared with the control group (n=15) in the lumbar spine (mean difference 1.9% [CI -0.9% to 4.6%]), total hip (mean difference 0.7% [CI -2.2% to 3.5%]) and distal forearm (mean difference 1.7% [CI -2.2% to 5.5%]), but these changes did not reach statistical significance. There was also a trend towards a reduction in bone turnover in the treatment group.
Calcium and vitamin D supplementation reduced the rate of bone turnover and bone loss in adult patients with cystic fibrosis, but these changes did not reach statistical significance. These data suggest that a longer term trial of this simple intervention would be justified.
Journal of Cystic Fibrosis 01/2005; 3(4):233-6. · 3.19 Impact Factor
