The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation.

BACKGROUND: Respiratory viruses have become increasingly recognised as important agents in pulmonary exacerbations in infants and children with CF. The aim of this study was to determine the prevalence of respiratory viruses during acute pulmonary exacerbations in adults and compare the severity of these exacerbations with non-viral associated exacerbations. METHODS: This was a retrospective case control study. Viral throat swabs were taken from all patients presenting with an acute pulmonary exacerbation requiring intravenous antibiotic treatment over a 12 month period. RESULTS: There were 432 pulmonary exacerbations in 180 adults. A positive viral PCR in 42 exacerbations indicated a prevalence of 9.7%. The commonest virus isolated was rhinovirus (n = 29, 69%) with influenza A/H1N1 in seven patients (16.7%). Exacerbations associated with a positive viral PCR had a greater fall in lung function at presentation with higher levels of inflammatory markers. They received more days of intravenous antibiotics, showed less response to treatment and had a shorter time to next pulmonary exacerbation compared to matched controls. CONCLUSION: Viral associated pulmonary exacerbations in adults with CF are associated with more severe pulmonary involvement and respond less well to standard treatment.

Enteral tube feeding in adults with cystic fibrosis; patient choice and impact on long term outcomes.

BACKGROUND: Enteral tube feeding (ETF) has been evaluated in paediatric and mixed child and adult populations with cystic fibrosis, demonstrating positive outcomes from 6 months to 2 years post insertion. No studies have examined the longer term nutritional and clinical outcomes in an exclusively adult population with cystic fibrosis or compared the outcomes for those who meet standard criteria and opt to undertake or decline ETF. METHODS: Twenty three out of 380 patients attending the Leeds Regional Adult CF unit fulfilled the standard criteria for commencing ETF (CF Trust, 2002) between 2004 and 2008. Weight, BMI, FEV1, FVC, CFRD, and number of intravenous antibiotic treatment days were collected at 1 year pre baseline, at baseline, and at 1, 2, and 3 years post baseline for all these patients whether they accepted or declined ETF. RESULTS: Seventeen of the 23 patients agreed to accept a programme of ETF, two of whom died within the first year of ETF. In the remaining patients (n=15), weight increased by 19.5% from baseline (p<0.001), BMI increased to within the normal range and lung function stabilised. There was no reduction in the requirement for intravenous antibiotic treatment. The six patients who declined ETF had a decline in lung function and no weight gain. CONCLUSION: Supplemental enteral tube feeding improves clinical outcomes when administered over 3 years, resulting in significant weight gain, a normal BMI and stabilisation of lung function. It does not reduce intravenous antibiotic treatment days. In contrast those patients eligible for, but who declined ETF, showed a deterioration in lung function and a failure to gain weight and to achieve normal BMI status.

Patient indicators of a pulmonary exacerbation: preliminary reports from school aged children map onto those of adults.

BACKGROUND: Despite the importance of identifying and managing a pulmonary exacerbation, and its use as an outcome measure in interventions, there is no standardised definition in cystic fibrosis. In achieving standardised criteria it is important to identify patient-reported indicators. METHODS: Interviews were undertaken with 35 school aged children. They reported symptoms experienced during a pulmonary exacerbation in two ways: the first symptoms they become aware of, and how they recognised when they were improving. Interviews were taped, transcribed verbatim and the data analysed thematically. RESULTS: For many children, the onset of an exacerbation was characterised by 'cold' symptoms, tiredness, and changes in cough. For those with moderate or severe disease, sleep disruption, activity induced breathlessness, changes in mood, sputum volume and lack of appetite were common. When describing improvement children focused initially on activities they were now able to perform accompanied by improvements in tiredness and cough. Those with moderate or severe disease also reported improvements in sleep and mood, breathlessness, sputum volume and colour. CONCLUSIONS: Child-reported indicators of a pulmonary exacerbation tend to map onto those reported by adults. These results provide the rationale for the development of a single scale for school age children and adults that could be sensitive to progressive stages of CF disease.

Cystic fibrosis co-existing with trisomy 21.

Previous reports of children with co-existence of cystic fibrosis and full trisomy 21 suggest a very poor prognosis, with the majority of cases dying in infancy and the oldest reported survivor being 6 years of age. We report the case of a young man with genetically confirmed trisomy 21 and homozygous for the F508del cystic fibrosis mutation. Despite the diagnosis of cystic fibrosis being delayed until the age of 2 years he has transitioned to adult services and is now 25 years of age. Currently he has poor lung function and a continuous ambulatory oxygen requirement.

Isolation of the fungus Geosmithia argillacea in sputum of people with cystic fibrosis.

We report the repeated isolation of the fungus Geosmithia argillacea from sputum samples of people with cystic fibrosis. Identification was based on morphology and DNA sequence analysis. Isolation of G. argillacea did not appear to be associated with clinical deterioration. The pathogenic potential of G. argillacea is discussed.

Serum tobramycin levels following delivery of tobramycin (Tobi) via eFlow advanced nebuliser in children with cystic fibrosis.

BACKGROUND: Safety and toxicity data for nebulised tobramycin are mainly derived from use of the Pari LC Plus nebuliser, yet many centres are now using advanced nebulisers, such as the eFlow. METHODS: Ten children (ages 2-16years) receiving 300mg TOBI via eFlow for clinical reasons participated. Serum tobramycin levels were obtained 1h post nebulisation. Nine provided samples for urinary NAG, and 10 underwent audiology. RESULTS: Tobramycin levels were >1mg/L in 3 children (maximum 3.8, 2 children aged 2years). Urine NAG/creatinine levels were raised (>0.94micromol/min/mmol) in 5 children, 1 of these had a tobramycin level of >1mg/L. One patient had high frequency hearing loss. CONCLUSION: Serum tobramycin levels over 1mg/L can occur 1h post 300mg TOBI delivered by eFlow. Raised urinary NAG levels suggest that some children may have some associated early renal toxicity.

An aerobiological model of aerosol survival of different strains of Pseudomonas aeruginosa isolated from people with cystic fibrosis.

Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detected up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

What defines a pulmonary exacerbation? The perceptions of adults with cystic fibrosis.

BACKGROUND: There is no standardised definition of a pulmonary exacerbation in cystic fibrosis (CF). In attempting to achieve standardised criteria it is important to identify patient-reported indicators. METHODS: Interviews were undertaken with 47 adults with CF. Participants were asked to report symptoms experienced during a pulmonary exacerbation in two ways: the first symptoms they become aware of, and how they subsequently recognised when they were improving. RESULTS: A range of systemic and respiratory symptoms were reported. Their relative importance varied by severity of disease. The severity and subsequent improvement of an exacerbation was often described as limitations on their activities. CONCLUSION: These preliminary data suggest that patient-reported indicators of a pulmonary exacerbation may not be the same for all adults with CF. Whether different indicators are associated with specific demographic or clinical variables remains to be evaluated.

Acute Burkholderia cenocepacia pyomyositis in a patient with cystic fibrosis.

INTRODUCTION: Extra-pulmonary complications of Burkholderia cepacia complex (Bcc) infection in patients with cystic fibrosis are unusual. To the best of the authors' knowledge no case of pyomyositis secondary to Bcc infection has been reported previously. CASE PRESENTATION: We report a case of pyomyositis of the forearm caused by Bcc infection in a patient with CF. We also briefly discuss the management of pyomyositis. CONCLUSION: Pyomyositis is a potential extra-pulmonary complication of Bcc infection in patients with CF. A high index of clinical suspicion is required to make a prompt diagnosis. Final diagnosis may need MRI. An early diagnosis, aggressive medical therapy, multidisciplinary care and timely surgical intervention are all essential for proper management of this condition.

Nutritional decline in cystic fibrosis related diabetes: the effect of intensive nutritional intervention.

BACKGROUND: Reports indicate that nutritional and respiratory decline occur up to four years prior to diagnosis of cystic fibrosis related diabetes (CFRD). Our aim was to establish whether intensive nutritional intervention prevents pre-diabetic nutritional decline in an adult population with CFRD. METHODS: 48 adult patients with CFRD were matched to 48 controls with CF, for age, gender and lung pathogen status. Nutritional and other clinical indices were recorded at annual intervals from six years before until two years after diagnosis. Data were also analysed to examine the impact of early and late acquisition of CFRD. RESULTS: No important differences in weight, height, body mass index (BMI), lung function or intravenous treatment were found between groups in the six years prior to diagnosis, nor any significant deviation over time. In those who developed diabetes, use of overnight enteral tube feeding (ETF) was four times as likely at the time of diagnosis, compared to controls [ETF 43.8% (CFRD) v 18.8% (CF Controls), OR 4.0, CI 1.3 to 16.4, p=0.01]. Age at onset of CFRD played a significant role in determining the pre-diabetic clinical course. Younger diabetics with continued growth at study onset (n=17) had a lower BMI from 2 years prior to diagnosis compared to controls [BMI 18.9 kg/m(2) (CFRD) v 20.8 kg/m(2) (CF Controls), diff=1.9, CI -0.1 to 3.7 p=0.04]. The BMI of older diabetics (completed growth at study onset) was equal to that of controls throughout. CONCLUSION: Pre-diabetic nutritional decline is not inevitable in adults with CFRD, but is influenced by age of onset. In the group overall, those with CFRD are more likely to require ETF from 2 years prior to diagnosis. Despite intensive nutritional intervention, patients who continue to grow throughout the pre-diabetic years, show a level of nutritional decline absent in older adults.

Decision making about reproduction and pregnancy by women with cystic fibrosis.

With significant improvements in longevity, women with cystic fibrosis are increasingly likely to consider pregnancy and parenthood. This article reviews the literature relating to medical and psychosocial research that informs the decision-making process these women undertake.

Exercise during childhood and adolescence: a prophylaxis against cystic fibrosis-related low bone mineral density? Exercise for bone health in children with cystic fibrosis.

Inadequate bone mineral accrual during growth and accelerated bone demineralisation in adulthood are recognised as additional and serious complications for patients with cystic fibrosis (CF). However, little attention has been given to preventative strategies for this population. Inadequate bone accrual during childhood and adolescence, and premature bone loss, lead to a failure to attain an optimal peak bone mass, osteoporosis and fracture in patients with CF. Pharmaceutical treatments may assist in the improvement of bone in patients with CF, but these are usually not preferable for use in children. Evidence indicates that regular, weight-bearing exercise significantly enhances bone accrual in healthy children. This paper reviews the literature concerning the potential for weight-bearing exercise to improve bone mineral accrual in children with CF. All relevant literature since 1979 was obtained and reviewed from the Medline, PubMed, Cochrane and PEDro data base. Evidence concerning the efficacy of exercise for bone health in CF is lacking. There have been no controlled trials investigating the value of weight-bearing exercise for bone accrual in children with CF. As exercise may offer an effective and enjoyable strategy to improve the bone development in children who have CF, exercise should be a high priority for randomised controlled trials in this population.

Enteral tube feeding for cystic fibrosis.

BACKGROUND: Enteral tube feeding is routinely used in many cystic fibrosis centres when weight for height percentage is less than 85%, when there has been weight loss for longer than a two-month period or when there has been no weight gain for two to three months (under five years old) or for six months (over five years old). OBJECTIVES: To examine the evidence that in people with cystic fibrosis supplemental enteral tube feeding improves nutritional status, respiratory function, and quality of life without significant adverse effects. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted the companies that market enteral feeds and reviewed their databases. Date of the most recent search of the Group's Cystic Fibrosis Trials Register: November 2007. SELECTION CRITERIA: All randomised controlled trials comparing supplemental enteral tube feeding for one month or longer with no specific intervention in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Thirteen trials were identified by the search; however, none were eligible for inclusion in this review. MAIN RESULTS: There are no trials included in this review. AUTHORS' CONCLUSIONS: Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in people with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy feeding, are invasive, expensive, and may have a negative effect on self-esteem and body image. Reported use of enteral tube feeding suggests that it results in nutritional and respiratory improvement and it is disappointing that their efficacy has not been fully assessed by randomised controlled trials. With the more frequent recommendations to use enteral tube feeding as an early rather than a late intervention, this systematic review identifies the need for a multicentre, randomised controlled trial assessing both efficacy and possible adverse effects of enteral tube feeding in cystic fibrosis. There are no trials included in the review and we have not identified any relevant trials up to November 2007. We therefore do not plan to update this review until new trials are published.

Respiratory exacerbations in childhood associated with compound heterozygosity Phe508del/Arg117His-7T of the cystic fibrosis transmembrane regulator gene.

UNLABELLED: Debate continues regarding the clinical implications for compound heterozygotes identified with Phe508del and Arg117His-7T mutations of the cystic fibrosis transmembrane regulator (CFTR) gene. We report respiratory exacerbations and airway culture of Staphylococcus aureus and Pseudomonas aeruginosa in a child with this genotype. CONCLUSION: The compound heterozygote cystic fibrosis (CF) mutation Phe508del with Arg117His-7T should not necessarily be considered benign in childhood.

Ten years of viral and non-bacterial serology in adults with cystic fibrosis.

Viral infections are associated with pulmonary exacerbations in children with cystic fibrosis (CF), but few studies have addressed the frequency in adults. This paper investigates the frequency and impact of viral infections in adults with CF receiving intravenous antibiotics. Pre- and post-treatment spirometry, inflammatory markers and antibody titres against influenza A, influenza B, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetti were analysed over a 10-year period. Non-bacterial infections were identified in 5.1% of 3156 courses of treatment. The annual incidence of admissions per patient associated with viral infection was 4.9%. The presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term. Adults with CF have a lower incidence of respiratory viral infections associated with pulmonary exacerbations requiring intravenous antibiotics compared to children and infants with CF.

Measurement of urinary N-acetyl-b-D-glucosaminidase in adult patients with cystic fibrosis: before, during and after treatment with intravenous antibiotics.

BACKGROUND: Patients with cystic fibrosis (CF) are at high risk from the nephrotoxic effects of intravenous antibiotics due to repeated and prolonged courses of therapy. Routine methods of monitoring renal injury are insensitive. N-acetyl-b-d-glucosaminidase (NAG) is a lysosomal enzyme present in the renal proximal tubular cells, with increased excretion an indicator of renal tubular dysfunction. METHODS: Urinary NAG, creatinine, serum creatinine, electrolytes and BUN were measured on days 1, 14 and at the first out-patient visit following treatment with tobramycin or colistin. Urinary NAG levels were corrected for urinary creatinine and expressed as a NAG ratio. Patients who received>1 course of intravenous antibiotics during the study period were included in a separate analysis of the cumulative effect of treatment. RESULTS: 88 patients (44 female, 31 with CFRD) completed a single course of intravenous antibiotics. 71 patients had urinary NAG levels at follow-up. The median time to follow-up was 50 days. Serum electrolytes, creatinine and BUN were normal throughout. A 3.5-fold increase in urinary NAG excretion was observed between day 1 and 14 and 46% of patients had an elevated NAG level at follow-up. A highly significant difference in NAG excretion was observed on day 14 for tobramycin vs. colistin (median 2.24 vs. 0.98, p<0.001). A significant difference in NAG excretion was seen in patients with CFRD at all measured time points. Patients with CFRD had a significantly worse clinical status and had received more days of intravenous antibiotics over the previous 6 years. In 20 (80%) of 25 patients who received>1 course of treatment during the study period, baseline NAG levels were significantly higher in subsequent courses (p<0.001). There was a significant correlation between previous exposure to colistin and baseline NAG levels (r=0.389, p<0.001). CONCLUSIONS: Both tobramycin and colistin cause acute renal tubular injury with a significant rise in urinary NAG excretion. Patients with CFRD seem to be at greatest risk of renal tubular damage. Cumulative damage is evident with repeated dosing. Previous exposure to nephrotoxic antibiotics, especially colistin, is associated with elevated baseline NAG levels. We recommend that colistin is reserved for patients with resistant Pseudomonas aeruginosa or those who are intolerant to tobramycin. Serial longitudinal NAG measurements may be useful in patients with CF, especially those with CFRD, to identify patients at risk of developing renal disease.

Low gammaglobulin subclass 2 levels in paediatric cystic fibrosis patients followed over a 2-year period.

The aim of this study was to relate serum immunoglobulin G2 subclass levels in a large paediatric population with cystic fibrosis, to clinical status and antibody levels to Haemophilus influenzae type b and Streptococcus pneumoniae and to observe any changes over a 2-year period. IgG subclasses were measured in 131 patients. Results were compared with levels from age-related normal population data. The following clinical data were collected at baseline and 2 years later; genotype: height, weight, and BMI z-scores: FEV1 (as percent predicted): Shwachman-Kulczcyki and Northern chest X-ray scores: Pseudomonas aeruginosa status. Antibody levels to H. influenzae type b and S. pneumoniae measured at baseline were related to IgG2 level. There was a reduction in the prevalence of low levels of IgG2 from 29% to 10% over the 2-year period. Low levels of IgG2 were not associated with any decline in clinical well-being. Low levels of IgG2 alone were associated with low antibody levels to S. pneumoniae. Low levels of IgG2 and low levels of antibody to H. influenzae and S. pneumoniae were not associated with any decline in clinical well-being. Children with high levels of IgG2 had worse lung function, worse Shwachman-Kulczcyki and Northern chest X-ray scores and higher levels of P. aeruginosa infection. Children with low IgG2 levels were not worse clinically compared to those with normal or high IgG2 levels. High IgG2 levels were associated with a worse clinical status.