A novel solution for severe urinary incontinence in women with cystic fibrosis.

BACKGROUND: To explore whether Tension-free Vaginal Tape offers a solution for women with cystic fibrosis who suffer from severe stress incontinence. METHODS: Four adults with cystic fibrosis were formally assessed by gynaecological and urological specialists, prior to hospital admission for surgery. RESULTS: The procedure was tolerated well by all patients. In three, leakage ceased completely. The fourth patient experienced considerable improvement in symptoms. CONCLUSIONS: Tension-free Vaginal Tape is a safe, effective and worthwhile solution for stress incontinence in females with cystic fibrosis.

Successful treatment of cepacia syndrome with combination nebulised and intravenous antibiotic therapy.

We report the case of successful treatment of a 31-year-old lady with cystic fibrosis and an en-bloc liver-pancreas transplant, who developed cepacia syndrome on a background of chronic infection with the ET12 epidemic strain of Burkholderia cenocepacia. Combination therapy with nebulised and intravenous meropenem and tobramycin led to clinical improvement with a return to baseline function and complete resolution of the acute chest X-ray changes.

Finding consensus on the physiotherapy management of asymptomatic infants with cystic fibrosis.

BACKGROUND: Babies with cystic fibrosis diagnosed by neonatal screening often display no overt signs of respiratory disease. The role of traditional routine daily chest physiotherapy in this particular group of babies is unclear and has generated considerable international debate. There is currently no evidence addressing this issue and present circumstances preclude a rigorous trial in the UK. This study aimed to provide expert consensus regarding the physiotherapy management of asymptomatic infants with CF. METHOD: A Delphi consensus method was used to gather and refine expert opinions of senior paediatric physiotherapists in the UK. Agreement was sought on 16 statements reflecting aspects of physiotherapy management in 'asymptomatic' babies with cystic fibrosis. RESULTS: Twenty-five senior paediatric physiotherapists from Specialist CF Centres throughout the UK participated in the study. Consensus was high amongst the respondents for 15 of the 16 statements. One statement failed to reach consensus. This related to the question of not routinely initiating a daily chest physiotherapy regimen in apparently healthy babies. Due to the lack of consensus an amendment to this statement was made, to allow a more flexible approach, where physiotherapists would not be obliged to initiate routine daily treatment in asymptomatic babies with CF, if they felt other another approach was justified. CONCLUSION: There was high consensus of opinion amongst senior physiotherapists in the UK on most aspects of the physiotherapy management of babies with CF. Consensus could not be achieved on whether routine daily chest physiotherapy is necessary in 'asymptomatic' babies. An agreed amendment to the original statement allows professionals to modify or change traditional practice with the sanction of their senior colleagues. The results of this process will be used by the Association of Chartered Physiotherapists in Cystic Fibrosis to form the basis of national clinical guidelines.

Protein kinase D distribution in normal human epidermis, basal cell carcinoma and psoriasis.

BACKGROUND: Keratinocytes undergo a defined programme of proliferation and differentiation during normal stratification of the epidermis. Anomalies in the signalling pathways controlling this process probably contribute to the pathogenesis of hyperproliferative dermatological diseases, including psoriasis and basal cell carcinoma (BCC). We have previously proposed that protein kinase D (PKD) is a proproliferative signalling enzyme in keratinocytes and have speculated that abnormalities in its levels or regulation may contribute to hyperproliferative disorders of the skin. OBJECTIVES: To determine if hyperproliferative human skin disorders are characterized by abnormal protein expression or distribution of PKD, normal human epidermis was compared with BCC and uninvolved and involved psoriatic epidermis. METHODS: To examine protein expression, immunohistochemical analysis of human samples and Western blotting of neoplastic mouse keratinocytes was performed. Western analysis of neoplastic mouse cells using a phosphospecific PKD antibody allowed estimation of PKD activation status. RESULTS: Normal human epidermis demonstrated predominant PKD protein expression in the stratum basalis, the proliferative epidermal compartment, with decreased relative expression throughout the suprabasal strata. Uninvolved psoriatic skin showed a similar pattern, but in contrast, psoriatic lesions demonstrated a diffuse distribution of PKD staining throughout all strata. The majority of BCCs examined showed significant PKD protein levels and, in those biopsies in which the levels could be compared, elevated PKD levels relative to normal epidermis. PKD levels and activation status were also increased in a neoplastic mouse keratinocyte cell line. CONCLUSIONS: PKD was elevated or misdistributed in the hyperproliferative human skin disorders, BCC and psoriasis, as well as neoplastic mouse keratinocytes. We speculate that PKD exerts proproliferative and/or antidifferentiative effects in the epidermis, and that anomalous distribution and/or activation of PKD may be involved in precipitating or sustaining the disease process in BCC and psoriasis.

Objective measurement of cough during pulmonary exacerbations in adults with cystic fibrosis.

BACKGROUND: Little is known about cough frequency in adults with cystic fibrosis (CF). This study aimed to determine (1) daytime and overnight cough rates in patients with CF at the beginning and end of a course of antibiotics for treatment of an exacerbation; (2) the relationship between cough frequencies and standard clinical measures of disease; and (3) the relationship between objective cough rates and the subjective assessment of cough. METHODS: Nineteen adult patients admitted with a pulmonary exacerbation performed daytime and overnight sound recordings on admission; 13 had repeat recordings prior to discharge. Coughs were manually quantified in cough seconds (time spent coughing). Patients subjectively scored their cough using a visual analogue scale (VAS) and numerical score. Lung function, C-reactive protein (CRP) levels, and sputum weights were recorded. RESULTS: Cough rates fell substantially with treatment; median fall in cough rate was 51.3% (IQR 32.3-77.5) (p<0.001) for daytime and 72.2% (28.6-90.1) (p = 0.049) for overnight. Multivariate regression analyses showed that forced expiratory volume in 1 second and CRP levels predicted overnight cough rates on admission. On discharge, sputum volume predicted daytime cough rates. Only the change in overnight VAS correlated with the change in objective cough rates. CONCLUSIONS: The cough rate significantly decreases with treatment of a pulmonary exacerbation in adults with CF. Lung function, sputum volume, and CRP influences the cough rate, with the effects differing from day to night and between admission and discharge. Subjective reporting of a nocturnal cough may indicate a pulmonary exacerbation of CF in adults.

Physiotherapy management of cystic fibrosis.

For many years physiotherapy for cystic fibrosis (CF) was synonymous with a daily routine of postural drainage and percussion. Improved longevity and a desire for independence, together with a clearer understanding of the pathophysiology of the disease, has led to the development of many airway clearance techniques. The contribution of 'chest' physiotherapy remained unchallenged until recent times when lack of robust evidence and the presentation of asymptomic infants and adults led some physiotherapists to question this traditional approach. As survival increases into the fourth and fifth decade unique complications have evolved and physiotherapy management is challenged with nonrespiratory aspects of treatment. This review will consider the evidence for, and current practice of airway clearance, the value of exercise and the emerging problems of musculoskeletal complications and incontinence.

Symptoms, lactate and exercise limitation at peak cycle ergometry in adults with cystic fibrosis.

The purpose of this study was to investigate symptoms, lactate accumulation and limiting factors at peak exercise in cystic fibrosis (CF) patients. In total, 104 CF adults attending an adult CF centre and 27 controls performed progressive cycle ergometry to a symptom-limited maximum. Measurements taken at peak exercise included: heart rate, ventilation, oxygen uptake, carbon dioxide output, oxygen saturation and blood lactate. Symptom scores of perceived breathlessness and muscle effort were recorded using Borg scales. The CF subjects had a lower mean body mass index, forced expiratory volume in one second (FEV(1)) and peak oxygen uptake than controls. Peak lactate concentrations were very similar to controls (mean+/-sd 6.8+/-2.0 mmol x L(-1) versus 7.4+/-1.0 mmol x L(-1)). Symptom scores were no different to controls for either breathlessness (4.5+/-2.0 versus 4.3+/-1.0) or perceived muscle effort (6.1+/-2.0 versus 6.5+/-1.0), with higher scores for muscle effort than breathlessness in both groups. In addition, peak ventilation was lower than the predicted maximum, and high peak heart rates were recorded supporting nonpulmonary factors as important in limiting peak exercise. Peak oxygen uptake was correlated with FEV(1). Comparison of CF subjects with mild or moderate pulmonary disease and controls revealed similar exercise responses. In contrast, those CF patients with severe lung disease (FEV(1) <40% predicted) had significantly higher breathlessness, lower muscle effort scores, lower peak lactate, lower peak heart rate and a mean ventilation exceeding predicted, thus confirming that ventilation was the major factor limiting exercise. In conclusion, cystic fibrosis subjects have a reduced peak exercise capacity, but their exercise response is similar to controls in generating high blood-lactate concentrations and symptoms of muscle effort in excess of dyspnoea. Nonpulmonary factors influence peak performance more in those without severe disease.

Individualised unsupervised exercise training in adults with cystic fibrosis: a 1 year randomised controlled trial.

BACKGROUND: Short term studies of exercise training have shown benefits in cystic fibrosis. Transferring exercise programmes to the community and sustaining them long term is a challenge for the patient. The effectiveness of an individualised unsupervised home based exercise programme was examined in adults with cystic fibrosis over a 1 year period. METHODS: Subjects were randomised to undertake three sessions per week of upper and lower body exercise based on individualised preferences (n = 30) or to a control group (n = 18). They were evaluated at baseline and at 12 months. The primary outcome measure was improved fitness as assessed by change in blood lactate concentration at the end of an identical constant work rate for both arm and leg ergometric testing. Secondary outcome measurements were heart rate and pulmonary function. RESULTS: For leg exercise, significant differences were seen at 12 months between the active and control groups in the mean (SE) change in blood lactate levels (-0.38 (0.23) mmol/l v 0.45 (0.25) mmol/l, p<0.05) and heart rate (-4.8 (2.5) bpm v 3.4 (2.5) bpm, p<0.05), confirming a training effect. For arm ergometry there was no change in lactate levels at 12 months but there was a significant difference in forced vital capacity (46 (72) ml v -167 (68) ml, p<0.05). CONCLUSIONS: A training effect, as measured by a reduction in lactate levels and heart rate, can be achieved with unsupervised individualised home exercise in adults with cystic fibrosis. A benefit to pulmonary function was observed and together these findings suggest that exercise programmes should be encouraged as an important component of care in cystic fibrosis.

Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in cystic fibrosis.

INTRODUCTION: Burkholderia cepacia infection has been associated with a poor prognosis for patients with cystic fibrosis (CF). It is now recognised that organisms classified as B cepacia comprise a number of distinct genomic species each known as a genomovar of the B cepacia complex (BCC). The outcome of infection for CF patients with individual genomovars is unknown. The clinical outcome of infection with the two most commonly isolated genomovars (B cenocepacia and B multivorans) was studied at a specialist CF centre between 1982 and 2003. METHODS: The numbers of patients who progressed from initial to chronic infection were assessed. Control groups were created by matching patients with chronic BCC infection by percentage forced expiratory volume in 1 second with patients with Pseudomonas aeruginosa infection. Outcome measures were survival time, deaths from "cepacia syndrome", rate of decline in spirometry and body mass index (BMI), and treatment requirements. RESULTS: Forty nine patients had an initial infection with either B multivorans (n = 16) or B cenocepacia (n = 33); 8/16 and 31/33, respectively, developed chronic infection (p<0.001). Deaths from "cepacia syndrome" occurred in both BCC groups. Patients with B cenocepacia infection had a shorter survival than patients with P aeruginosa infection (p = 0.01). There was no difference in survival between CF patients infected with B multivorans and P aeruginosa. There were no observed differences in changes in spirometry and BMI or treatment requirements between the BCC groups and respective controls. CONCLUSION: In CF, the genomovar status of BCC may influence both the likelihood of progression from initial to chronic infection and the overall survival of the patients.

Inflammatory markers in cystic fibrosis patients with transmissible Pseudomonas aeruginosa.

Chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF) leads to a damaging host inflammatory response. There are an increasing number of reports of P. aeruginosa cross-infection at CF centres. The clinical significance of acquisition of a transmissible strain for patients who already harbour P. aeruginosa is unclear. In this study, levels of inflammatory markers in clinically stable adult CF patients who harbour transmissible and sporadic strains of P. aeruginosa have been compared. Patients with CF and chronic P. aeruginosa infection were grouped into those who harbour a transmissible P. aeruginosa and those who harbour their own sporadic strains. Total white cell and differential counts, sputum neutrophil elastase (NE), interleukin (IL)-8, tumour necrosis factor (TNF)-alpha, plasma IL-6 and NE/alpha1-antitrypsin complexes, serum C-reactive protein, and urine TNF receptor 1 were all measured in clinically stable patients 4-6 weeks following completion of intravenous antibiotic therapy. The two groups (both n=20) were well matched for per cent predicted forced expiratory volume in one second, per cent predicted forced vital capacity and body mass index. There were no significant differences in levels of white cell counts or inflammatory markers between the two groups. At times of clinical stability, cystic fibrosis patients infected with transmissible Pseudomonas aeruginosa do not have a heightened inflammatory response above that of those harbouring sporadic strains.

Identification of airborne dissemination of epidemic multiresistant strains of Pseudomonas aeruginosa at a CF centre during a cross infection outbreak.

BACKGROUND: Chronic Pseudomonas aeruginosa infection is a major cause of morbidity and mortality for individuals with cystic fibrosis (CF). P aeruginosa cross infection outbreaks have recently been reported at CF holiday camps and specialist centres. The mechanism of cross infection is unknown. A study was performed to look for the presence of epidemic strains of P aeruginosa in the environment of a CF centre during a cross infection outbreak and to examine their potential modes of spread between patients. METHODS: Microbiological sampling of the environment of the CF facility was performed, including room air sampling. Individual P aeruginosa strains were identified by bacterial fingerprinting. The typing patterns were compared with those of epidemic strains responsible for cross infection among the patients. RESULTS: Epidemic P aeruginosa strains were isolated from room air when patients performed spirometric tests, nebulisation, and airway clearance, but were not present in other areas of the inanimate environment of the CF centre. CONCLUSIONS: Aerosol dissemination may be the most important factor in patient-to-patient spread of epidemic strains of P aeruginosa during recent cross infection outbreaks at adult CF centres.

Treatment of urinary incontinence in cystic fibrosis.

BACKGROUND: Urinary incontinence (UI) is a newly recognised problem in cystic fibrosis. Whilst prevalence is well documented, there are no reports of assessment and treatment of the problem. METHODS: A previous study reports the prevalence of UI in women with CF to be 51/75 (68%). Nineteen women subsequently requested help for the problem and were referred to a physiotherapist specialising in women's health. A digital assessment was performed to measure pelvic floor muscle strength and endurance. An individualised programme of pelvic floor muscle exercises (PFME) was taught based on the assessment. A questionnaire addressed issues of assessment and treatment. RESULTS: 12 women were assessed. The median (range) age, FEV1% predicted and BMI were 20.9 (19.3-46.1) years, 45.9 (14.8-82.7) and 20.5 (16.1-26.0), respectively. The median strength of the pelvic floor muscle was moderate (Oxford Scale grade 3) with a hold time (endurance) of 5 s. At reassessment (median time 13.1 weeks), there was an improvement in endurance (P = 0.04), with no change in strength. This was supported by a subjective improvement in symptoms. Patients found the exercises were difficult to perform, difficult to fit into their treatment programme and adherence was poor. CONCLUSIONS: PFME are effective at improving endurance and reducing leakage over the short-term. Women are reluctant to be assessed and the CF team should provide support and encouragement with treatment. Long-term outcome and the mechanisms of UI in this group of patients need further evaluation.

Increased treatment requirements of patients with cystic fibrosis who harbour a highly transmissible strain of Pseudomonas aeruginosa.

BACKGROUND: A group of patients who harbour the same highly transmissible strain of Pseudomonas aeruginosa were identified at a cystic fibrosis (CF) centre. Isolates of this strain display a number of unusual phenotypic features including resistance to most typical antipseudomonal antibiotics. A study was undertaken to see if there was a difference in treatment requirements between CF patients with chronic infection with their own unique P aeruginosa strains (group 1) and those who harbour a highly transmissible strain (group 2). METHODS: Data on treatment requirements for the year 2000 were collected from the case records of CF patients with chronic P aeruginosa infection who had received inpatient treatment. Patients co-infected with Burkholderia cepacia or other highly transmissible strains of P aeruginosa were excluded. RESULTS: There were 2/56 and 3/22 deaths in groups 1 and 2, respectively; these patients were excluded from the analysis. No difference was found between the two groups for mean age, % predicted forced expiratory volume in 1 second (FEV(1)), % predicted forced vital capacity (FVC), and body mass index. Patients in group 2 had a greater median (range) number of intravenous antibiotic days (60 (17-216) v 33 (4-237) days; p=0.01), inpatient days (39 (7-183) v 16 (1-172) days; p<0.01), and inpatient episodes (3 (1-9) v 2 (1-6); p<0.01), and more respiratory exacerbations (mean (SD) 8.2 (3.4) v 6.1 (3.2); p=0.01). CONCLUSIONS: Patients who harbour the highly transmissible P aeruginosa strain have a greater treatment burden than patients with CF who harbour their own unique strains. These findings support the need for microbiological surveillance for highly transmissible P aeruginosa and the implementation of infection control measures to prevent cross infection.

PCR-based detection and identification of Burkholderia cepacia complex pathogens in sputum from cystic fibrosis patients.

PCR amplification of the recA gene followed by restriction fragment length polymorphism (RFLP) analysis was investigated for the rapid detection and identification of Burkholderia cepacia complex genomovars directly from sputum. Successful amplification of the B. cepacia complex recA gene from cystic fibrosis (CF) patient sputum samples containing B. cepacia genomovar I, Burkholderia multivorans, B. cepacia genomovar III, Burkholderia stabilis, and Burkholderia vietnamiensis was demonstrated. In addition, the genomovar identifications determined directly from sputum were the same as those obtained after selective culturing. Sensitivity experiments revealed that recA-based PCR could reliably detect B. cepacia complex organisms to concentrations of 10(6) CFU g of sputum(-1). To fully assess the diagnostic value of the method, sputum samples from 100 CF patients were screened for B. cepacia complex infection by selective culturing and recA-based PCR. Selective culturing identified 19 samples with presumptive B. cepacia complex infection, which was corroborated by phenotypic analyses. Of the culture-positive sputum samples, 17 were also detected directly by recA-based PCR, while 2 samples were negative. The isolates cultured from both recA-negative sputum samples were subsequently identified as Burkholderia gladioli. RFLP analysis of the recA amplicons revealed 2 patients (12%) infected with B. multivorans, 11 patients (65%) infected with B. cepacia genomovar III-A, and 4 patients (23%) infected with B. cepacia genomovar III-B. These results demonstrate the potential of recA-based PCR-RFLP analysis for the rapid detection and identification of B. cepacia complex genomovars directly from sputum. Where the sensitivity of the assay proves a limitation, sputum samples can be analyzed by selective culturing followed by recA-based analysis of the isolate.

Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic.

We initiated a prospective surveillance study to investigate possible Pseudomonas aeruginosa cross-infection in our cystic fibrosis centre. We characterised isolates by pyocin typing and pulsed-field gel electrophoresis. 22 (14%) of 154 patients with chronic P aeruginosa had isolates with similar and new pyocin and pulsed-field gel electrophoresis types. The shared isolates showed unusual phenotypic features: they were non-pigmented, non-motile, and resistant to a number of antipseudomonal antibiotics. Cross-infection by a multiresistant P aeruginosa strain has therefore occurred in patients attending our cystic fibrosis centre. We recommend microbiological surveillance in other cystic fibrosis centres.

Questionnaire survey of urinary incontinence in women with cystic fibrosis.

Cystic fibrosis is an inherited disease characterised by the production of infected secretions, and it requires lifelong daily treatment by airway clearance. We knew that some women attending our clinic for adults with cystic fibrosis leaked urine when performing airway clearance or spirometry, but they were dismissive during discussion and were rarely forthcoming about the problem. This study was designed to determine the prevalence of urinary incontinence in women with cystic fibrosis, to establish the importance of the problem as perceived by the patients, and to identify those women who wanted help.

Burkholderia cepacia: current clinical issues, environmental controversies and ethical dilemmas.

Burkholderia cepacia is a plant phytogen and is known as a hardy and versatile organism. Over the past two decades it has emerged as a pathogen in the cystic fibrosis (CF) community, with devastating effects. Pulmonary colonisation can lead to an accelerated decline in lung function. In some cases, it causes a rapid and progressive pneumonic illness termed "cepacia syndrome", which is untreatable and fatal. B. cepacia is inherently resistant to multiple antibiotics and highly transmissible and virulent strains have been identified. CF patients colonised with the organism have to be segregated from their peers to try to prevent cross-infection. However, the pathogenicity of B. cepacia is not limited to CF. Other groups, such as individuals with chronic granulomatous disease and immunocompromised patients are vulnerable and it has caused disease in healthy individuals. However, the agricultural and petrochemical industries are attempting to exploit properties of B. cepacia for use as a biopesticide and biodegradation agent. This article provides an up to date review of clinically based literature on the Burkholderia cepacia complex, highlighting clinical management issues for both cystic fibrosis and non-cystic fibrosis patients. The article also addresses the potential conflict between medicine and agriculture on plans to reintroduce strains of Burkholderia cepacia back into the environment.

Burkholderia gladioli: recurrent abscesses in a patient with cystic fibrosis.

We describe a case of an adult patient with cystic fibrosis who developed chronic pulmonary infection and multiple episodes of soft tissue abscesses with Burkholderia gladioli; this organism should be added to the list of potential pathogens for individuals with cystic fibrosis.