A.K. Webb

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.

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.

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.

Inflammatory related changes in bone mineral content in adults with cystic fibrosis

Background: Proinflammatory cytokines stimulate osteoclast activity and this could lead to increased bone resorption in patients with cystic fibrosis. The aim of this study was to determine whether markers of systemic inflammation are related to changes in bone mineral content (BMC) in adults with cystic fibrosis. Methods: Total body BMC was assessed by dual energy x ray absorptiometry in 100 patients (54 male) of mean (SD) age 25.6 (7.1) years and forced expiratory volume in 1 second (FEV1) 61.8 (24.1)% predicted on recruitment to the study and 1 year later. Blood was also taken at these time points to measure markers of systemic inflammation. Results: After 1 year BMC had reduced by 16.1 (62.1) g, p = 0.01; (0.6 (2.8)%). The change in BMC was related to mean levels of interleukin (IL)-6 (rs = −0.39, p<0.001) and C reactive protein (rs = −0.34, p = 0.002), intravenous antibiotic use (rs = −0.27, p = 0.006) and oral corticosteroid use (rs = −0.20, p = 0.045). Urinary markers of osteoclast activity were also related to IL-6 (rs  =  0.27, p = 0.02). Multiple linear regression revealed that IL-6 (coefficient –2.2 (95% CI –3.4 to –1.0) per pg/ml, p = 0.001), colonisation with Burkholderia cepacia (coefficient –46.8 (95% CI –75.5 to –18.1), p = 0.002), and annual change in BMI (coefficient 15.4 (95% CI 3.6 to 27.2) per kg/m2, p = 0.011) were independently significant predictors of annual change in BMC. Conclusions: These data suggest a pathophysiological mechanism by which chronic pulmonary infection results in bone loss in patients with cystic fibrosis.

A prospective study of change in bone mineral density over one year in adults with cystic fibrosis

Background: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. To identify appropriate therapeutic strategies and the optimal time for intervention, it is necessary to document the natural history of cystic fibrosis related low BMD. Methods: 114 adults with cystic fibrosis underwent bone densitometry a median (25–75% interquartile range) of 12 (12–13) months after initial assessment of bone density. BMD was measured in the lumbar spine, femoral neck, total hip, and distal forearm on recruitment to the trial and at follow up. Results: In patients ≤24 years of age (n=55, mean (SD) age 19.5 (2.6) years) in whom an annual increase in BMD would normally be expected, BMD increased by a mean (95% CI) 2.9% (1.6 to 4.2) per year in the distal forearm (p<0.001), but decreased by 2.5% (95% CI –3.8 to –1.2) per year in the femoral neck (p<0.001) and by 2.2% (95% CI –3.3 to –1.0) per year in the total hip (p<0.001). In patients ≥25 years of age (n=59, mean (SD) age 30.3 (5.4) years) in whom no annual change in BMD would normally be expected, BMD decreased by 1.9% (95% CI –2.9 to –0.8) per year in the femoral neck (p<0.001), by 1.5% (95% CI –2.4 to –0.6) per year in the total hip (p=0.001), and by 0.8% (95% CI –1.5 to –0.1) per year in the distal forearm (p=0.026). There was no significant annual change in lumbar spine BMD in either patient cohort. Conclusions: Reduced rates of bone accretion and accelerated rates of bone loss explain the high prevalence of low BMD in adults with cystic fibrosis.

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 (FEV1) and peak oxygen uptake than controls. Peak lactate concentrations were very similar to controls (mean±sd 6.8±2.0 mmol·L−1 versus 7.4±1.0 mmol·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 FEV1. 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 (FEV1 <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.

Long term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis

Background: Several studies have suggested that clinical outcomes in adults with cystic fibrosis (CF) are equivalent after home and hospital treatment with intravenous antibiotics, but these studies were small and selective and only considered one course of treatment. Methods: A retrospective longitudinal study was performed to compare the clinical outcome over a period of 1 year of all patients attending the Manchester Adult CF Unit who received intravenous antibiotics at home or in hospital. The primary outcome measure was percentage change in forced expiratory volume in 1 second (FEV1) at the end of the 1 year period. Baseline “best” and “average” FEV1 values were established for each patient for the year before the study. The secondary outcome measures were percentage changes in forced vital capacity (FVC) and body weight. Results: A total of 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year there had been a mean percentage decline in FEV1 compared with the baseline “average” for patients treated mostly at home but an improvement in patients treated mostly in hospital (Tukey’s HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). For all patients there was a mean percentage decline in FEV1 from the baseline “best” value. For each course of treatment the mean percentage improvements in FEV1 at the end of the course from the start of the course were significantly higher for patients treated in hospital than for those treated at home. Conclusions: Clinical outcome, as defined by spirometric parameters and body weight, was better after a course of treatment in hospital than after home treatment, and this benefit was maintained over 1 year of treatment. The results suggest that patients treated at home need closer supervision.

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.

Allergic bronchopulmonary aspergillosis in lung allograft recipients

Following lung transplantation for end-stage cystic fibrosis, two male patients presented with shortness of breath, peripheral blood eosinophilia and segmental lung collapse. At bronchoscopy, each had bronchial mucous plugging containing Aspergillus fumigatus. This finding was associated with a systemic eosinophilia and skin test positivity to Aspergillus. Augmented steroid therapy resulted in the successful resolution of the symptoms. We believe that these are the first reported cases of allergic bronchopulmonary aspergillosis in lung allograft recipients.

Pneumothorax in adults with cystic fibrosis dependent on nasal intermittent positive pressure ventilation (NIPPV): a management dilemma

The management of pneumothorax in three adult patients with cystic fibrosis dependent on nasal intermittent positive pressure ventilation is described.