Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased. A number of centres have adopted a policy of regular (three monthly) rather than on demand intravenous antipseudomonal antibiotics. More widespread bacterial antibiotic resistance has resulted from this increased antibiotic use. Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity. A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis. METHODS: Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were randomised to receive treatment for 12 days with either colistin (2 MU tds intravenously) alone or with a second anti-pseudomonal antibiotic. Comparisons of the absolute values of respiratory function tests on days 1, 5, and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures. Patient's weight, clinical and chest radiographic scores, and peripheral blood markers of inflammation were also documented. The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values. Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes, creatinine clearance, and ward urine testing. Neurotoxicity was monitored by direct questioning for symptoms. RESULTS: Fifty three patients, 18 of whom entered the study twice, were enrolled. The mean forced expiratory volume in one second (FEV1) increased significantly in both groups, mean forced vital capacity (FVC) only with dual therapy. Both groups showed a non-significant increase in overnight oxygen saturation. All patients showed clinical improvement. Thirty seven adverse neurological events (two severe) were reported in 33 patients in the monotherapy group and 37 (none severe) in 36 patients in the dual therapy group. One patient withdrew because of severe weakness and dizziness. All other adverse neurological events were well tolerated and resolved during or shortly after treatment. Significant changes were seen in mean serum urea levels in both groups, but in only four patients to a level above the normal range, and in creatinine clearance in the dual therapy group. At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study. CONCLUSIONS: Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis. Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity. Changes in renal function should be monitored.

Functional iron deficiency in adults with cystic fibrosis.

Functional iron deficiency (transferrin saturation < 16%) was found in 44 (62%) of 71 adult cystic fibrosis (CF) patients. Haemoglobin concentration and mean cell volume were lower in iron-deficient patients, in whom there was a non-significant trend for lower serum ferritin. Ten iron-deficient patients and two patients with transferrin saturation > = 16% (normal iron) were anaemic. There were no significant differences between iron-deficient and normal-iron patients in intake of calories, protein, iron and vitamin C as determined by 4-day records of dietary intake. Dietary iron deficiency is not an important factor in functional iron deficiency in adult CF patients. Impairment of absorption by exogenous pancreatic enzyme supplements is unlikely to be significant as enzyme intake was the same in the two groups. Iron-deficient patients had lower Shwachman-Kulczycki scores and lower percent predicted forced expiratory volume in 1 s (FEV1% predicted) and forced vital capacity (FVC% predicted). There was a non-significant trend for higher values of white cell count and plasma viscosity in the iron-deficient group. Chronic inflammation is likely to be the primary cause of functional iron deficiency in adult CF patients. Fifteen patients completed 3-month courses of oral iron replacement with no deterioration in pulmonary function, but with no effect on haemoglobin concentration.

Compliance with treatment in adult patients with cystic fibrosis.

BACKGROUND: Patients with chronic disease comply with about 50% of their treatment. The complex and time consuming daily drug regimens needed in the care of adult patients with cystic fibrosis encourage non-compliance with prescribed treatments. Understanding the reasons for, and the extent of, non-compliance is essential for a realistic appraisal of the patient's condition and sensible planning of future treatment programmes. METHODS: Patients were invited to complete a questionnaire which asked about their compliance with daily treatment. The data were used to calculate a compliance score, the percentage of prescribed treatment taken, and to examine patient attitudes to each individual prescription. An assessment score derived from consultant, cystic fibrosis research fellow, specialist nurse, and physiotherapist ratings of patient compliance was compared with the compliance score. Both scores were correlated with patient characteristics and disease severity, and the compliance score was also correlated with the patient's knowledge of cystic fibrosis. RESULTS: More than half the patients claimed to take more than 80% of their treatments. Compliance with individual treatments varied according to their perceived unpleasantness and degree of infringement on daily activities. The most common reason given for omitting treatment was forgetfulness. Professional carers were poor judges of patient compliance. There was no correlation between compliance and patients' sociodemographic characteristics or their knowledge about cystic fibrosis. CONCLUSIONS: Non-compliance is universal and should be recognised as normal behaviour. There are no reliable criteria for predicting any patient's level of compliance. Treatment protocols should be planned around individual patient's requirements, modifying treatment ideals where necessary according to the exigency and pattern of that patient's lifestyle.

Knowledge of adult patients with cystic fibrosis about their illness.

BACKGROUND: Adult patients need to understand their illness if the locus of control is to move from doctor to patient. Previous studies have shown important misconceptions and gaps in patients' knowledge about cystic fibrosis. METHODS: Patients were invited to complete a multiple choice questionnaire covering all major aspects of cystic fibrosis. The questionnaire score was compared with a predicted score derived from the consultant, cystic fibrosis fellow, nurse, and physiotherapist ratings of patient knowledge. Data were obtained to provide a comprehensive patient profile and disease severity score. Both scores were tested for any associations with patient characteristics. RESULTS: Although patients had good general knowledge about the aspects of cystic fibrosis that impacted most on their daily lives--that is, respiratory and gastrointestinal problems--important gaps and misconceptions in these areas were still present. Knowledge and understanding of genetic and reproductive issues and the less common complications of cystic fibrosis were only moderate. Older more severely affected patients, and those who had more contact with the hospital caring team, had better multiple choice questionnaire knowledge scores. Professional carers were poor judges of the knowledge of individual patients. CONCLUSIONS: Important gaps persist into adult life in the knowledge patients with cystic fibrosis have about their illness. Objective assessment of these deficits is required so that each patient can be counselled according to his or her needs.

Munchausen syndrome by proxy abuse: a foundation for adult Munchausen syndrome.

Symptoms fabricated by the mother, and abnormal maternal pressurising of medical staff, resulted in misinterpretation of sweat test results and a diagnosis of cystic fibrosis in a two year old child. Her mother refused to accept later medical evidence which irrefutably showed this diagnosis to be wrong. The child was extensively investigated and for most of her childhood was treated for pancreatic malabsorption. She progressed from an innocent child victim of Munchausen Syndrome by Proxy abuse to an accomplice in her mother's deception, and finally to adult Munchausen Syndrome behaviour. Munchausen Syndrome by Proxy abuse may programme a child into developing adult Munchausen Syndrome.

Nocturnal oxygen desaturation and spirometric parameters in adults with cystic fibrosis.

BACKGROUND: Correction of nocturnal hypoxaemia in patients with cystic fibrosis may delay the development of pulmonary hypertension. Descriptive statistics used for nocturnal arterial oxygen saturation (SpO2) lack uniformity. The relationship between SpO2 and spirometric parameters has not previously been explored in a large number of exacerbations in adult patients with cystic fibrosis. METHODS: Over a 21 month period overnight SpO2, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were recorded on admission and discharge in 120 treatments of pulmonary exacerbations in 47 patients with cystic fibrosis who did not receive supplemental oxygen during recording. Nocturnal SpO2 was related to spirometric parameters for the whole group and individually in 11 patients, each of whom had at least five treatments. RESULTS: There was a close linear relationship between the percentage of the recording spent with SpO2 < 90% and mean overnight SpO2. Mean SpO2 correlated moderately with percentage predicted FEV1(%FEV1), r = 0.6, and poorly with percentage predicted FVC (%FVC), r = 0.34. The relationship between mean SpO2 and % FEV1 was non-linear at mean SpO2 < 89%, but approximated to linearity above this value. After exclusion of treatments with mean SpO2 < 89% the regression relationship between mean SpO2 and %FEV1 was the same on admission and discharge. Individual correlation coefficients of mean SpO2 versus % FEV1 in the 11 patients with repeated treatments ranged from 0.57 to 0.77. The slopes of the regression lines did not differ, with a pooled slope of 0.116, but the intercepts varied widely. CONCLUSIONS: In patients with cystic fibrosis mean overnight SpO2 can be substituted for percentage of recording < 90%. The relationship between mean SpO2 and percentage predicted FEV1 is non-linear at low values of SpO2 and is not influenced by treatment of pulmonary exacerbations. Patients with cystic fibrosis desaturate at a uniform rate compared with percentage predicted FEV1, but the value of FEV1 at which desaturation first occurs varies between patients. The spirometric values do not accurately predict nocturnal desaturation in a cystic fibrosis population, but FEV1 is a useful guide in individual patients with moderate desaturation.

Home versus hospital intravenous antibiotic therapy in the treatment of young adults with cystic fibrosis.

We wanted to investigate whether home intravenous antibiotic treatment of pulmonary exacerbations of cystic fibrosis is as effective as treatment in hospital. The case records of all patients attending the Leeds adult cystic fibrosis clinic were reviewed to identify those who had received home intravenous antibiotic treatment. All home treatments undertaken were included. For each home treatment, the temporally closest hospital treatment for that patient was then selected for comparison and the changes with treatment in peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), C-reactive protein (CRP), plasma viscosity, total white cell count, absolute neutrophil count, total immunoglobulin G (IgG) concentration, chest X-ray score (Northern), clinical score, Shwachman-Kulczyki score and weight were analysed for differences between home treatment and hospital treatment. Fifty one paired home/hospital treatments in 25 patients were compared. The improvement in total white cell count was found to be significantly greater in the hospital group, but the difference was very small. The improvements in absolute neutrophil count, and all the other measured variables, were the same in the two groups. Treatment of exacerbations of cystic fibrosis at home or in hospital is, thus, equally effective given proper patient selection and adequate monitoring of the response to treatment.

The chest radiograph in cystic fibrosis: a new scoring system compared with the Chrispin-Norman and Brasfield scores.

BACKGROUND: Scoring systems for the chest radiograph in cystic fibrosis are used to compare patients and different treatment regimens, and to monitor respiratory disease in individual patients. The Northern chest radiograph score was designed to allow one person to assess the radiological features of lung involvement in cystic fibrosis in as simple, rapid and equally reproducible manner as the established Chrispin and Norman, and Brasfield scoring systems. METHODS: Forty five chest radiographs were scored by 10 physicians with a special interest in cystic fibrosis according to the Brasfield and Northern methods, and by five pairs of physicians according to the Chrispin-Norman criteria. Three individuals and two pairs rescored the radiographs after an interval of 3-5 months. The Northern score was performed with and without a lateral view, using the original posteroanterior radiograph. RESULTS: The Northern score showed a better agreement between observers for the ranking of the radiographs. It was equally well related to respiratory function tests, the Shwachman-Kulczycki score of overall clinical status, and in its discrimination between different radiographs as the other two scoring systems. The Northern score performed equally well with or without a lateral film. CONCLUSIONS: The Northern system fulfils the requirements of a chest radiograph score more successfully than the Chrispin-Norman or Brasfield systems, and does not require a lateral film.

Patient and parental attitudes toward genetic screening and its implications at an adult cystic fibrosis centre.

General population screening for cystic fibrosis carrier status in the United Kingdom would detect 72% of at-risk couples. Proper counselling would allow these couples to make informed reproductive choices, including the possibility of prenatal diagnosis and the termination of an affected pregnancy. However, children with cystic fibrosis born in this decade, given optimum treatment, now have an average life expectancy of 40 years, and there is no unanimity of opinion on how, where, when, or even if, screening should be offered. The purpose of this questionnaire-based study was to examine the attitudes of an adult clinic population who have grown up with cystic fibrosis, and of their parents, towards genetic screening programmes and the controversies and ethical dilemmas surrounding such programmes in cystic fibrosis. Both patients and parents supported prenatal screening (88% and 90%) and the option of terminating an affected pregnancy (68% and 84%). Only 22% of patients and 10% of parents felt that screening should be limited to families with a history of cystic fibrosis, and 19% and 6%, respectively, that prenatal diagnosis should be restricted to those with a previous child with cystic fibrosis. Despite the negative aspects of any screening programme and the acknowledged ethical problems peculiar to cystic fibrosis, the conclusion of our patients and parents who have lived intimately with the illness is that there should be the option of utilising information available from genetic screening for cystic fibrosis to guide reproductive choices. Pilot programmes to define the optimum management of such screening should continue.